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Antiviral Chemical Compounds

                                                                                                                                                                                                                                  Download data

ENTITY POTENCY SAFETY_INFORMATION EVIDENCE PMID
2-alkyl-2-aminoadamantane derivatives with sufficient adductsActivity against p2009 influenza AThe results indicate that 2-alkyl-2-aminoadamantane derivatives with sufficient adducts can persistently block p2009 influenza A in vitro through an alternative mechanism.24793875
Naphthyridone 3 (HM13N)Inhibit the HIV-1A 1,8-naphthyridone derivative targets the HIV-1 Tat-mediated transcription and potently inhibits the HIV-1 replication. The emergence of multidrug resistant HIV-1 strains and the inability of the HAART to eradicate HIV-1 virus from infected patients demand new drugs able to interfere with an alternative step of the replicative cycle.19958026
Conjugation of D4T with 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine)Anti-HIV activityConjugation of D4T with 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine)-type reverse transcriptase inhibitors via the SATE prodrug approach. This paper reports the synthesis and the antiviral activities of new double-prodrugs against HIV based on the known mixed SATE (S-acyl-2-thioethyl) prodrug approach.15715487
2-cyano-3-acrylamide small-moleculeActivity against murine norovirus (MNV) and ListeriaAnti-infective Activity of 2-Cyano-3-Acrylamide Inhibitors with Improved Drug-Like Properties against Two Intracellular Pathogens. Due to the rise of antibiotic resistance and the small number of effective antiviral drugs, new approaches for treating infectious diseases are urgently needed.27139470
2,4-diarylaniline analogs (DAANs) derivatives 9a-9eHIV-1 reverse transcriptase inhibitors, compound 9e not exhibited extremely high potency against wild-type virus (EC(50) 0.53 nM) and several resistant viral strains (EC(50) 0.36-3.9 nM)Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors. The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resistant strains, aqueous solubility, and metabolic stability.22406117
UC 38, analog of oxathiin carboxanilideAnti-HIV activityBiological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor. UC 38, a simple analog of oxathiin carboxanilide, UC 84, lacking the oxathiin ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1-induced cell killing and HIV replication in a variety of human cell lines, as well as in human peripheral blood lymphocytes and macrophages.8558446
Pyridazinone derivative, compound 3711Inhibits hepatitis B virusPyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection.26349829
1,1,3-trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine (TTD) derivatives, i.e., 2-(3-fluorobenzyl)-4-cyanomethylen-l,1,3-trioxo-2H,4H- thieno [3,4-e] [1,2,4] thiadiazine) (QM96639)Inhibit human immunodeficiency virus (HIV) type 1 [HIV-1 (IIIB)] at concentration 0.09 microM1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity. We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs).9517942
BAY 57-1293Against HSV infectionPotent in vivo antiviral activity of the herpes simplex virus primase-helicase inhibitor BAY 57-1293. BAY 57-1293 belongs to a new class of antiviral compounds and inhibits replication of herpes simplex virus (HSV) type 1 and type 2 in the nanomolar range in vitro by abrogating the enzymatic activity of the viral primase-helicase complex.12019088
Urea-PETT (phenylethylthiazolylthiourea)HIV-1 inhibitorUrea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues. The further development of allosteric HIV-1 RT inhibitors in the urea analogue series of PETT (phenylethylthiazolylthiourea) derivatives is described here. The series includes derivatives with an ethyl linker (1-5) and racemic (6-16) and enantiomeric (17-20) cis-cyclopropane compounds.10514285
Diphenyl heterocyclic compounds(R706)hepatitis C virus (HCV)We conclude that R803 and related heterocyclic compounds constitute a new class of HCV-specific inhibitors that could potentially be developed as a treatment for HCV infection.18227176
Crown-Like Oxotricyclic Core as the P2-LigandHIV-1 inhibitorDesign and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown-Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV Variants. Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1 protease inhibitors are reported.28418652
Neoechinulin B and its analoguesActivity against H1N1 virusA class of prenylated indole diketopiperazine alkaloids including 15 new compounds namely rubrumlines A-O obtained from marine-derived fungus Eurotium rubrum, were tested against influenza A/WSN/33 virus. Neoechinulin B (18) exerted potent inhibition against H1N1 virus infected in MDCK cells, and is able to inhibit a panel of influenza virus strains including amantadine- and oseltamivir-resistant clinical isolates.25681711
Meso-tetrakis-(3,5-dicarboxy-4,4'-biphenyl) porphyrinActivity against hepatitis C virus (HCV)A novel class of meso-tetrakis-porphyrin derivatives exhibits potent activities against hepatitis C virus genotype 1b replicons in vitro. Recent years have seen the rapid advancement of new therapeutic agents against hepatitis C virus (HCV) in response to the need for treatment that is unmet by interferon (IFN)-based therapies.19901090
Combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavirHIV-1 inhibitorDiscovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV. A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir.16828558
PTC725Targets the hepatitis C Virus NS4B proteinIdentification of PTC725, an orally bioavailable small molecule that selectively targets the hepatitis C Virus NS4B protein. While new direct-acting antiviral agents for the treatment of chronic hepatitis C virus (HCV) infection have been approved, there is a continued need for novel antiviral agents that act on new targets and can be used in combination with current therapies to enhance efficacy and to restrict the emergence of drug-resistant viral variants.23629699
Acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic aminesNS3 helicase of hepatitis C virus (HCV) with IC(50) range from 1.5 to 20 microMSynthesis of new acridone derivatives, inhibitors of NS3 helicase, which efficiently and specifically inhibit subgenomic HCV replication. A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV).20337460
Novel compounds generated by merging pharmacophores of salicylate and catechol [2,3-dihydroxybenzamide (5a), structural modifications on the 5a scaffold with carboxamide and the piperidin-1-ylsulfonyl substituted at the phenyl ring to generate (5p), N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u)]HIV-1 inhibitor, 5p, IC(50)=5 microM, 5u IC(50) value of 8 microMDesign of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently.21778063
Bicyclic hydroxy-1H-pyrrolopyridine-trionesHIV-1 integrase inhibitorsBicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. We report herein bicyclic hydroxy-1H-pyrrolopyridine-triones as a new family of HIV-1 integrase inhibitors that were efficiently prepared using a key 'Pummerer cyclization deprotonation cycloaddition' cascade of imidosulfoxides.22107736
N-(2-phenylethyl)-N'-(2-thiazolyl)thiourea (LY73497)Inhibit HIV-1 but not HIV-2The PETT series, a new class of potent nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. To identify the minimal structural elements necessary for biological activity, the rigid tricyclic nucleus of the known human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor tetrahydroimidazobenzodiazepinthione was subjected to systematic bond disconnection to obtain simpler structures.7574525
1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracilsHIV-1 non-nucleoside reverse transcriptase inhibitorsDesign, synthesis, and biological evaluation of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors with an improved drug resistance profile. Because the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using nevirapine and 18 (TNK-651) as reference compounds.22283377
Amidine 6 and guanidine 7Activity against oseltamivir-resistant influenza virusesDevelopment of novel potent orally bioavailable oseltamivir derivatives active against resistant influenza A. With the emergence of oseltamivir-resistant influenza viruses and in view of a highly pathogenic flu pandemic, it is important to develop new anti-influenza agents. Several 5-guanidino- and 5-amidino-based oseltamivir derivatives were synthesized and profiled for their anti-influenza activity and in vitro and in vivo PK properties. Amidine 6 and guanidine 7 were comparably effective against a panel of different A/H1N1 and A/H3N2 strains and also inhibited mutant A/H1N1 neuraminidase. Among different prodrug strategies pursued, a simple amidoxime ethyl ester (9) exhibited a superior PK profile with an oral bioavailability of 31% (rats), which is comparable to oseltamivir (36%). Thus, bioisosteric replacement of the 5-guanidine with an acetamidine-in the form of its N-hydroxy prodrug-successfully tackled the two key limitations of currently used NA inhibitors, as exemplified with oseltamivir.24422530
PL-100Potent inhibition of HIV-1 protease and viral replication in vitro (K(i), approximately 36 pM, and 50% effective concentration [EC(50)], approximately 16 nM, respectively)In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Despite the success of highly active antiretroviral therapy, the current emergence and spread of drug-resistant variants of human immunodeficiency virus (HIV) stress the need for new inhibitors with distinct properties.17638694
1H-1,2,3-triazole-4-carboxamide derivative 3bAnti-influenza A viruses, H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strainsDesign, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein. The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development.22332894
3-Hydroxypyrimidine-2,4-dione-5-N-benzylcarboxamidesInhibit HIV-1 Integrase and RNase H3-Hydroxypyrimidine-2,4-dione-5-N-benzylcarboxamides Potently Inhibit HIV-1 Integrase and RNase H. On the basis of our previously reported 3-hydroxypyrimidine-2,4-dione (HPD) core, we have designed and synthesized a new integrase strand transfer (INST) inhibitor type featuring a 5-N-benzylcarboxamide moiety. Significantly, the 6-alkylamino variant of this new chemotype consistently conferred low nanomolar inhibitory activity against HIV-1.27283261
4-Benzyloxy-gamma-sultone (4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives ) derivativesAgainst human cytomegalovirus (HCMV) and varicella zoster virus (VZV)4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus. We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system.19226140
(3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7Activity against multidrug-resistant HIV-1 variantsDesign and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity studies and biological evaluation. The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described.21194227
New series of fused heteroaromatic sulfonamidesAgainst HIV-1Design of HIV-1 protease inhibitors active on multidrug-resistant virus. On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides.15771440
4-substituted 1,5-diarylanilines( three most promising compounds 14e, 14h, and 15h)Activity against HIV-1, EC(50) values ranging from 0.2 to 10 nMDesign, synthesis, and preclinical evaluations of novel 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) drug candidates. Twenty-one new 4-substituted diarylaniline compounds (DAANs) (series 13, 14, and 15) were designed, synthesized, and evaluated against wild-type and drug resistant HIV-1 viral strains.22856541
MP-134 and MP-167Inhibitors of HIV type 1 proteaseDesign, synthesis, and resistance patterns of MP-134 and MP-167, two novel inhibitors of HIV type 1 protease. Inhibitors of HIV-1 protease represent a new class of antiretroviral compounds.8825619
1-aryl-4,6-diamino-1,2-dihydrotriazine derivativesInhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC50 = 0.060 ?M)We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme.28477572
1H-benzo[de]isoquinoline-1,3(2H)-dionesInhibitors of HCV NS5B polymerase.Herein, we present 1H-benzo[de]isoquinoline-1,3(2H)-diones as a new series of selective inhibitors of HCV NS5B polymerase.19877603
Imide derivatives of 3-nitro-1.8-naphthalic acidActivity against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5)Imide derivatives of 3-nitro-1.8-naphthalic acid: their inhibitory activity against DNA viruses. The antiviral action of a new drug, 5-amino-2-(dimethylaminoethyl)-benzo-[de]-isoquinolin-1.3-dione has been studied against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5) grown in Vero cells.6299235
SPD754 (also known as AVX-754)Activity against HIV-1 and HIV-2 in vitro and against recombinant viruses containing thymidine analogue mutations (TAMs)In vitro activity of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI), against 215 HIV-1 isolates resistant to other NRTIs.16245645
9-phenylcyclohepta[d]pyrimidinedione derivativesInhibit HIV-1 replicationInhibitory activity of 9-phenylcyclohepta[d]pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors. BACKGROUND: The non-nucleoside reverse transcriptase inhibitor (NNRTI), as a major component of the highly active antiretroviral therapy (HAART) to HIV-1 (human immunodeficiency virus type 1) infected patients, required the development of new NNRTIs with improved resistance profile and decreased toxicity.21569631
New diarylaniline (DAAN) analoguesAnti-HIV potency, especially against the E138KThree series (6, 13, and 14) of new diarylaniline (DAAN) analogues were designed, synthesized, and evaluated for anti-HIV potency, especially against the E138K viral strain with a major mutation conferring resistance to the new-generation non-nucleoside reverse transcriptase inhibitor drug rilpivirine (1b).27070547
Pyrrolidine-3,4-bis-N-benzyl-sulfonamidesThe most promising candidate exhibited a K(i) of 74 nM towards a wild-type HIV proteaseRecently, symmetric pyrrolidine-3,4-bis-N-benzyl-sulfonamides have been developed as a new class of HIV-1 protease inhibitors.18692068
Compounds HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands?HIV-1 protease inhibitorsStructure-based design, synthesis, and structure-activity relationship studies of HIV-1 protease inhibitors incorporating phenyloxazolidinones. A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized.20958050
Diarylpyrimidine (DAPY)Nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1. This paper reports the synthesis and the antiviral properties of new diarylpyrimidine (DAPY) compounds as nonnucleoside reverse transcriptase inhibitors (NNRTIs).15771449
2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4(3H)-one (S-DABO) derivativesTarget at the non-nucleoside reverse transcriptase inhibitors resistant HIV-1 strainThe anti-HIV activity of three 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4 (3H)-one derivatives acting as non-nucleoside reverse transcriptase inhibitor in vitro. It was recently shown that several new synthetic 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4(3H)-one (S-DABO) derivatives demonstrated anti-HIV-1 activity.21348416
Lactoside compoundsAgainst HIV-1Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection. Despite significant improvements, antiretroviral therapies against HIV-1 are plagued by a high frequency of therapeutic failures that have been associated with acquisition of drug resistance.22064534
New derivative of bevirimatHIV-1 maturation inhibitorSynthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site. Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction.23399723
Alizarine analogues K-49 and KNA-53Inhibitors of the HIV-1, IC(50) values for both RT-associated functions of ? 10 micromAlizarine derivatives as new dual inhibitors of the HIV-1 reverse transcriptase-associated DNA polymerase and RNase H activities effective also on the RNase H activity of non-nucleoside resistant reverse transcriptases. HIV-1 reverse transcriptase (RT) has two associated activities, DNA polymerase and RNase H, both essential for viral replication and validated drug targets.21348941
Proteasome inhibitor VL-01Reduction of influenza virusAntiviral activity of the proteasome inhibitor VL-01 against influenza A viruses. The appearance of highly pathogenic avian influenza A viruses of the H5N1 subtype being able to infect humans and the 2009 H1N1 pandemic reveals the urgent need for new and efficient countermeasures against these viruses.21777621
2-phenylimidazopyridinesHerpes infection2-phenylimidazopyridines, a new series of Golgi compounds with potent antiviral activity. Drugs targeted to viral proteins are highly vulnerable to the development of resistant strains.17973358
9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62)Activity against herpes simplex virus types 1 and 2A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2. A novel nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62), was found to have potent antiviral activity against herpes simplex virus types 1 and 2 at concentrations well below cytotoxic levels.6289741
1-(omega-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ringInhibitors of Hepatitis C Virus replicationHere, we describe new 1-(?-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ring as potential antiviral drugs against HCV. A detailed structure-activity relationship revealed that the most active compounds were the N(3)-substituted uracil derivatives containing 6-(4-bromophenoxy)hexyl or 8-(4-bromophenoxy)octyl fragment at N(1) position.27406141
Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring HIV-1 non-nucleoside reverse transcriptase inhibitorsIndolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity.17803291
2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c),Anti-HSV-1Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%. . CONCLUSION: We succeeded in this context to synthesize a new series of potent fused pyrimidine derivatives as anti-HSV-1.29219053
5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidinesAnti-human immunodeficiency virus (HIV)Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines. OBJECTIVES: To discover new potent and selective anti-human immunodeficiency virus (HIV) acyclic nucleoside phosphonate (ANP) drugs with in vivo antiretroviral activity.17124193
SJ-3366Inhibited the entry of both HIV-1 and HIV-2SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2. We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6).11158731
Benzamide derivative N-[1-(7-tert-Butyl-1H-indol-3-ylmethyl)-2-(4-cyclopropanecarbonyl-3-methyl-piperazin-1-yl)-2-oxo-ethyl]-4-nitro-benzamide (SP-10)Reduces HIV-1 infectivity (IC50 = 0.036 nM)We investigated the in vitro efficacy, safety and mechanism of action of the benzamide derivative N-[1-(7-tert-Butyl-1H-indol-3-ylmethyl)-2-(4-cyclopropanecarbonyl-3-methyl-pipera zin-1-yl)-2-oxo-ethyl]-4-nitro-benzamide (SP-10), a potential new HIV treatment. When HIV-1-responsive engineered HeLa cells were pre-incubated for 48 h with either SP-10 or zidovudine (AZT), SP-10 was able to inhibit viral replication at much lower concentrations (IC50 = 0.036 nM) than AZT (IC50 = 27.4 nM).17249247
1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidineActivity against Influenza A virus strains (IC50 = 7.7 microM)A series of (R)- and (S)-isomers of new adamantane-substituted heterocycles (1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidine) with potent activity against rimantadine-resistant strains of influenza A virus were synthesized through the transformation of adamantyl-substituted N-Boc-homoallylamines 8 into piperidine-2,4-diones 11 through the cyclic bromourethanes 9 and key intermediate enol esters 10.28338150
Thiophene[3,2-d]pyrimidine DerivativesHIV-1 Non-nucleoside Reverse Transcriptase InhibitorsStructure-Based Optimization of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants. In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells. Compound 25a was exceptionally potent against the whole viral panel, affording 3-4-fold enhancement of in vitro antiviral potency against WT, L100I, K103N, Y181C, Y188L, E138K, and K103N+Y181C and 10-fold enhancement against F227L+V106A relative to the reference drug etravirine (ETV) in the same cellular assay. Overall, the results indicate that 25a is a promising new drug candidate for treatment of HIV-1 infection.28481112
Triazolo[4,5-g]quinoline derivatives (compounds 1-6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1)Activity against NNRTI-resistant HIV-1 mutantsActivity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants. In this preliminary study we report the antiviral screening of triazolo[4,5-g]quinoline derivatives (compounds 1-6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective, promising activity in cell-based assays against HIV-1wt and clinically relevant NNRTI resistant mutants.19775780
PHA767491Activity against human herpes simplex virus(both HSV-1 and HSV-2)PHA767491 potently blocked the proliferation of HSV in cells, as well as HSV induced cell death. Further, we found that PHA767491 strongly inhibited HSV infection post viral entry. Moreover, PHA767491 reduced the expression of viral genes required for DNA synthesis including UL30/42 DNA polymerase and UL5/8/52 helicase-primase complex. Thus, PHA767491 could be a promising agent for the development of new anti-HSV therapy.28320320
Alternariol 5-O-Methyl EtherInhibits HIV-1 Integration by Blocking NuclearMicrobial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration by Blocking Nuclear Import of the Pre-Integration Complex. While Highly Active Antiretroviral Therapy (HAART) has significantly decreased the mortality of human immunodeficiency virus (HIV)-infected patients, emerging drug resistance to approved HIV-1 integrase inhibitors highlights the need to develop new antivirals with novel mechanisms of action.28489061
5,6-dimethylxanthenone-4-acetic acid (DMXAA)Activity against H1N1 influenzaThe anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo. The 2009 outbreak of pandemic H1N1 influenza, increased drug resistance, and the significant delay in obtaining adequate numbers of vaccine doses have heightened awareness of the need to develop new antiviral drugs that can be used prophylactically or therapeutically.21084628
2,3-dihydrobenzofuran derivativesHepatitis C Virus (HCV) NS5A InhibitorsDiscovery of Chromane Containing Hepatitis C Virus (HCV) NS5A Inhibitors with Improved Potency against Resistance-Associated Variants. This effort, incorporating the C-1 fluoro substitution at the tetracyclic indole core, led to the discovery of a new series of NS5A inhibitors, such as compounds 14 and 25-28, with significantly improved potency against resistance-associated variants, such as GT2b, GT1a Y93H, and GT1a L31V.27792320
Moronic acid and other triterpene derivativesMoronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 microM against NL4-3, 0.021 microM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 microM against FHR-2 (an HIV strain resistant to 8)Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.16942019
n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole derivativesCoxsackie B5 virusCytotoxicity tests show that many of these substances are well tolerated by the VERO cells.The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus.11169164
TLT35HIV-1 infection preventionHere we reported the design of a novel chimera protein-based fusion inhibitor targeting gp41, TLT35, that uses a flexible 35-mer linker to couple T20 and T1144, the first and next generation HIV-1 fusion inhibitors, respectively.21690094
Benzophenone template compounds 70h (GW678248)70h has in vitro antiviral assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapineStructure-activity relationship studies of novel benzophenones leading to the discovery of a potent, next generation HIV nonnucleoside reverse transcriptase inhibitor. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies..16420058
ThiazolidenebenzenesulfonamidesActivity against nevirapine-resistant virus, HIV-1(IIIB-R)Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors.15519161
SA-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoateActivity against influenza A virusA target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. SA-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. Based on these favourable findings, SA-2, a novel anti-influenza agent, with its potent anti-influenza activity in vitro and in vivo, could be a promising antiviral for the treatment of infection of influenza A viruses, including oseltamivir-resistant mutants.26802558
JTK-853Nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase.Collectively, these data demonstrate that JTK-853 is a potent and novel nonnucleoside palm site-binding HCV polymerase inhibitor, suggesting JTK-853 as a potentially useful agent in combination with other DAAs for treatment of HCV infections.22615294
1R,2R-dicamphanoyl-3,3-dimethydihydropyrano[2,3-c]xanthen-7(1H)-one (DCX)Reverse transcriptase (RT) inhibitor-resistant HIV-1 (RTMDR-1) strains.Design, synthesis, and evaluation of 1R,2R-dicamphanoyl-3,3-dimethyldihydropyrano-[2,3-c]xanthen-7(1H)-one (DCX) derivatives as novel anti-HIV agents. In this study, 1R,2R-dicamphanoyl-3,3-dimethydihydropyrano[2,3-c]xanthen-7(1H)-one (DCX) derivatives were designed and synthesized as novel anti-HIV agents against both wild-type and non-nucleoside reverse transcriptase (RT) inhibitor-resistant HIV-1 (RTMDR-1) strains.22063755
Benzimidazole-related compoundTo prevent chikungunya virus (CHIKV) infectionDiscovery of a novel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus. Screening of chemical compound libraries were performed and one candidate, a benzimidazole-related compound designated Compound-A was found to inhibit infection by several CHIKV strains and a Sindbis virus strain at nanomolar concentrations.28236746
141W94 (VX-478) in combination with other antiretroviral agentsHIV-1 protease inhibitor with an IC50 of 0.08 microM against HIV-1 (strain IIIB) and a mean IC50 of 0.012 microM against six HIV clinical isolates.In vitro antiviral activity of 141W94 (VX-478) in combination with other antiretroviral agents. 141W94 (VX-478) is a novel HIV-1 protease inhibitor with an IC50 of 0.08 microM against HIV-1 (strain IIIB) and a mean IC50 of 0.012 microM against six HIV clinical isolates. 141W94 was synergistic on the basis of isobologram analysis with each of the following reverse transcriptase inhibitors: AZT, 935U83, 524W91, 1592U89 and ddl, 141W94 was also synergistic with saquinavir and additive with either indinavir or ritonavir.8721545
Alkylamidophospholipid analoguesAnti-human immunodeficiency virus type 1 agentsIn vitro evaluation and characterization of newly designed alkylamidophospholipid analogues as anti-human immunodeficiency virus type 1 agents. Our laboratories first reported two novel classes of complex synthetic lipids, including alkylamidophosphocholines (PC lipid; CP-51) and alkylamidophosphate ester-linked lipid-AZT conjugates (lipid-AZT conjugates; CP-92), with selective and potent activity against human immunodeficiency virus type 1 (HIV-1).9875387
6-{4-[(biphenyl-2-ylcarbonyl) amino]benzoyl}-N-cyclopropyl-5,6-dihydro-4H-thieno[3,2-d][1]benzazepine-2-carboxamide (YM-53403).The EC(50) value 0.20 microM, was about 100-fold more potent than ribavirin.YM-53403, a unique anti-respiratory syncytial virus agent with a novel mechanism of action15708639
Stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate) (stampidine)Anti-HIV activityWe have evaluated the clinical potential of stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate(stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, as a new anti-human immunodeficiency virus (anti-HIV) agent, by examining its acute, subacute, and chronic toxicity profile in mice as well as by testing its antiviral activity in a surrogate human peripheral blood lymphocyte (Hu-PBL)-SCID mouse model of human AIDS.12384347
Alkenyldiarylmethanes( most potent of these proved to be 3',3"-dibromo-4',4"-dimethoxy-5'5"-bis(methoxycarbonyl)-1,1-diphenyl-1-+ ++heptene)Anti-HIV-1 activitySynthesis and biological evaluation of certain alkenyldiarylmethanes as anti-HIV-1 agents which act as non-nucleoside reverse transcriptase inhibitors. Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized.8759644
17-amino-17-demethoxygeldanamycin derivativesInhibited duckling hepatitis B virus DNA replicationThe 17-amino-17-demethoxygeldanamycin derivatives could be novel agents with potential antiviral activity.20710066
6-methyl-7-substituted-7-deaza purine analoguesCompounds 5x (IC50 = 5.88 microM and 6.95 microM for H1N1 and H3N2, respectively) and 5z (IC50 = 3.95 microM and 3.61 microM for H1N1 and H3N2, respectively) demonstrated potent anti-influenza A activity.Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents.26802557
1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanolAverage 50% inhibitory concentration [IC50], 0.26 microM for 1592U891592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.9145874
Cytidine analogue, FNC (2'-deoxy-2'-?-fluoro-4'-azidocytidine)Strongly inhibit human HBV and duck HBV (DHBV) replication in vitro and in vivo, respectively.A novel cytidine analogue, FNC (2'-deoxy-2'-?-fluoro-4'-azidocytidine), was recently shown to strongly inhibit human HBV and duck HBV (DHBV) replication in vitro and in vivo, respectively.22910281
2'-deoxy-3'-thiacytidine (BCH-189)Activity against five different strains of human immunodeficiency virus type 1 (HIV-1) (mean 50% inhibitory dose, 0.73 microM)less toxic than AZT in cell cultureAnti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. We describe a novel nucleoside analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom.1929298
2',3'-didehydro-3'-deoxy-4'-ethynylthymidineActivity anti-human immunodeficiency virus type 1 (HIV-1)Weak cytotoxicity in cell culturesAnti-human immunodeficiency virus type 1 activity and resistance profile of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine in vitro. 2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T) has been identified as a novel nucleoside analog with potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity and weak cytotoxicity in cell cultures. 4'-Ed4T proved to be 5- to 10-fold more active than its structurally related compound, stavudine (d4T).16048947
GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosphonic acid]Activity against nucleoside-resistant variants of human immunodeficiency virus type 1Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosphonic acid] is a novel ribose-modified human immunodeficiency virus type 1 (HIV-1) nucleotide reverse transcriptase (RT) inhibitor (NRTI) selected from a series of nucleoside phosphonate analogs for its favorable in vitro biological properties including (i) a low potential for mitochondrial toxicity, (ii) a minimal cytotoxicity in renal proximal tubule cells and other cell types, (iii) synergy in combination with other antiretrovirals, and (iv) a unique resistance profile against multiple NRTI-resistant HIV-1 strains.18056282
2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]-pyrimidineActivity against multidrug-resistant hepatitis B virus mutantsIn vitro activity of 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]-pyrimidine against multidrug-resistant hepatitis B virus mutants. The susceptibilities of drug-resistant hepatitis B virus (HBV) mutants to lamivudine, adefovir, tenofovir, entecavir, and 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]-pyrimidine (PMEO-DAPym), a novel acyclic pyrimidine analogue, were assessed in vitro.17371827
Pleconaril and [(biphenyloxy)propyl]isoxazole derivatives with substitutions in the central ringActivity against pleconaril-resistant coxsackievirus B3New pleconaril and [(biphenyloxy)propyl]isoxazole derivatives with substitutions in the central ring exhibit antiviral activity against pleconaril-resistant coxsackievirus B3. In the present study, novel analogues with different substitutions in the central phenoxy group were synthesized to study their influence on anti-CVB3 activity with the aim to overcome pleconaril resistance.18840470
6-(3-trifluoromethylbenzyl) and 6-(fluorobenzyl)Activity against HIV-1 wild type and mutants resistant to non-nucleoside RT inhibitorsSynthesis and antiviral evaluation of 6-(trifluoromethylbenzyl) and 6-(fluorobenzyl) analogues of HIV drugs emivirine and GCA-186. The present study describes the synthesis and antiviral evaluation of a series of novel 6-(3-trifluoromethylbenzyl) and 6-(fluorobenzyl) analogues of the HIV drugs emivirine and GCA-186.18161905
2-amino thiazole [T157602 and its analogs]Inhibitor of herpes simplex virus (HSV) DNA replicationT157602 and its analogs represent a novel class of specific and reversible anti-HSV agents eliciting their inhibitory effects on HSV replication by interacting with the UL5 helicase.9696789
4-[1-hydroxy-2-(4,5-dimethoxy-2-nitrophenyl)ethyl]benzonitrile (LPCRW_0005)Inhibits rhinovirus replicationA novel benzonitrile analogue inhibits rhinovirus replication.24948704
6-PMEO 2,4-diaminopyrimidine and 6-PMPO 2,4-diaminopyrimidine derivativesPotent activity against human immunodeficiency virus (HIV) in the laboratoryAntiretrovirus activity of a novel class of acyclic pyrimidine nucleoside phosphonates. A novel class of acyclic nucleoside phosphonates has been discovered in which the base consists of a pyrimidine preferably containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy (PMEO) or a 2-(phosphonomethoxy)propoxy (PMPO) group at C-6.12069973
3-Biphenylimidazo[1,2-a]pyridines or [1,2-b]pyridazines and analoguesActivity against bovine viral diarrhoea virus (BVDV) and hepatitis C virus (HCV)3-Biphenylimidazo[1,2-a]pyridines or [1,2-b]pyridazines and analogues, novel Flaviviridae inhibitors. Using Ttou 84 as starting point, a novel class of biphenyl derivatives of imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine was designed to optimize the inhibitory properties on the replication of the bovine viral diarrhoea virus (BVDV) and hepatitis C virus (HCV).23665801
Beta-d-2'-deoxy-2'-?-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977)Inhibitors of the HCV NS5B polymeraseDiscovery of a Beta-d-2'-deoxy-2'-?-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. Hepatitis C virus (HCV) is a global health problem requiring novel approaches for effective treatment of this disease.20845908
BAY 38-4766Inhibitor of human cytomegalovirus (HCMV)Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action. As a representative of a novel inhibitory approach, the non-nucleosidic BAY 38-4766 was identified as a highly selective inhibitor of human cytomegalovirus (HCMV).11733458
Elaidic acid ganciclovir (E-GCV)Activity against laboratory and clinical strains of herpes simplex type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) in human embryonic lung fibroblasts, IC(50) value of E-GCV for HSV-1 strain KOS being 0.07 nMAntiviral activity of ganciclovir elaidic acid ester against herpesviruses10771080
Brecanavir, a novel tyrosyl-based arylsulfonamideAnti-HIV activityBrecanavir, a novel tyrosyl-based arylsulfonamide, high-affinity, human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), has been evaluated for anti-HIV activity in several in vitro assays.17620375
GW678248Anti-human immunodeficiency virus type 1GW678248, a novel nonnucleoside reverse transcriptase inhibitor, has been evaluated for anti-human immunodeficiency virus activity in a variety of in vitro assays against laboratory strains and clinical isolates.16251284
PD0084430Non-nucleoside inhibitor of human cytomegalovirus replicationPD0084430: a non-nucleoside inhibitor of human cytomegalovirus replication in vitro. A novel, non-nucleoside inhibitor of HCMV replication, PD0084430, was identified in a screening assay using the HCMV beta-galactosidase recombinant RC256.11675146
Naphthyridinone GSK364735Potently inhibited recombinant human immunodeficiency virus type 1 (HIV-1) integrase in a strand transfer assay (mean 50% inhibitory concentration +/- standard deviation, 8 +/- 2 nM).The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral.18160521
6-(indol-2-yl)pyridine-3-sulfonamidesInhibit HCV RNA replication in the HCV replicon cell culture assayDiscovery of novel HCV inhibitors: synthesis and biological activity of 6-(indol-2-yl)pyridine-3-sulfonamides targeting hepatitis C virus NS4B.23683597
GRL-02031Effective against laboratory HIV-1 strains and primary clinical isolates, including subtypes A, B, C, and E (50% effective concentration [EC(50)] range, 0.015 to 0.038 microM)Minimal cytotoxicity (50% cytotoxic concentration, >100 microM in CD4(+) MT-2 cells)GRL-02031, a novel nonpeptidic protease inhibitor (PI) containing a stereochemically defined fused cyclopentanyltetrahydrofuran potent against multi-PI-resistant human immunodeficiency virus type 1 in vitro.18955518
Benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI chemical seriesCompound A inhibited HIV-1 RT in a primer extension assay (50% inhibitory concentration, 2.6 nM) but had no measurable activity against human DNA polymerase ? at 10 microM. It potently inhibited HIV-1 replication in vitro (50% effective concentration, 1.5 nM)Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series23545531
Phosphonylmethoxyalkyl derivatives of adenineEquine herpesvirus 1Effective chemotherapy of equine herpesvirus 1 by phosphonylmethoxyalkyl derivatives of adenine demonstrated in a novel murine model for the disease.2163242
Substituted N-phenylbenzenesulphonamidesNon-nucleoside hepatitis C virus polymerase inhibitors with IC(50) values up to 40 nMHere we describe a novel non-nucleoside inhibitor (NNI) chemotype identified by screening: The substituted N-phenylbenzenesulphonamides (SPBS) which showed reversible inhibition of NS5B from HCV genotype 1b with IC(50) values up to 40 nM.22580131
Pyridinioalkanoyl thioesters (PATEs)Anti-HIV agents, EC(50) < 10 microMNon toxicSynthesis and biological properties of amino acid amide ligand-based pyridinioalkanoyl thioesters as anti-HIV agents.11886789
9-ArylpurinesThese compounds elicit activity against a variety of enteroviruses in the low microM range including Coxsackie virus A16, A21, A24, Coxsackie virus B3, and echovirus 9.9-Arylpurines as a novel class of enterovirus inhibitors. Here we report on a novel class of enterovirus inhibitors that can be structurally described as 9-arylpurines.19924996
Tricyclic nucleosides [9-benzylamino-3-(?-D-ribofuranosyl)-3H-imidazo[4',5':5,6]pyrido[2,3-b]pyrazine (15d)]Inhibited non-structural protein 5A (NS5A) of hepatitis C virus (HCV)Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism28245093
4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA)Inhibitor of HIV-1Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol.8540705
PNU-183792, a 4-oxo-dihydroquinolineActivity against human and animal herpesviruses, specifically inhibit herpesvirus polymerasesBroad-spectrum antiviral activity of PNU-183792, a 4-oxo-dihydroquinoline, against human and animal herpesviruses.11888654
Cyclohexyl carboxylic acid analogues [VX-787]Strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strainsDiscovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2.25019388
FP-21399 of bis(disulfonaphthalene) dimethoxybenzene classInhibitor of HIV-1FP-21399 is a novel compound of the bis(disulfonaphthalene) dimethoxybenzene class that blocks entry of HIV into CD4+ cells and blocks fusion of infected and noninfected CD4+ cells.9094135
Pirodavir (R 77975), a phenoxy-pyridazinamineBroad-spectrum antipicornaviral activityIn vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity. Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds.1317142
1,5-diphenylpyrazoleNonnucleoside HIV-1 reverse transcriptase inhibitorsNovel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. Through computationally directed broad screening, a novel 1, 5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered.10715167
SB 9200SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus, and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo.SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants. SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways.28303593
2,4,5-Trisubstituted thiazole derivativesTested on seven NNRTI-resistant HIV-1 strains, and all exhibited inhibitory effects with fold changes in IC50 ranging from 2.6 to 1112,4,5-Trisubstituted thiazole derivatives: a novel and potent class of non-nucleoside inhibitors of wild type and mutant HIV-1 reverse transcriptase.25072874
2,6-Bis(benzimidazol-2-yl)pyridine (BBP/CSFA-0)BBP/CSFA-0 inhibits the in vitro replication of the classical swine fever virus (CSFV) with an EC50 of 0.330 +/-.25microM. BBP/CSFA-0 proved in vitro inactive against the hepatitis C virus, that belongs like BVDV and CSFV to the family of Flaviviridae.Substituted 2,6-bis(benzimidazol-2-yl)pyridines: a novel chemical class of pestivirus inhibitors that targets a hot spot for inhibition of pestivirus replication in the RNA-dependent RNA polymerase.24680957
Bictegravir (GS-9883)Anti-HIV-1, specifically targets IN strand transfer activity (50% inhibitory concentration [IC50] of 7.5 ? 0.3 nM) and HIV-1 integration in cellsBIC exhibits potent and selective in vitro antiretroviral activity in both T-cell lines and primary human T lymphocytes, with 50% effective concentrations ranging from 1.5 to 2.4 nM and selectivity indices up to 8,700 relative to cytotoxicity.Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile.27645238
6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivativesActive in human immunodeficiency virus type 1 (HIV-1) infectionAnti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives. Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of current combination therapies for human immunodeficiency virus type 1 (HIV-1) infection.22290950
ASP2151Activity aginst varicella-zoster virus and herpes simplex virus types 1 and 2ASP2151, a novel helicase-primase inhibitor, possesses antiviral activity against varicella-zoster virus and herpes simplex virus types 1 and 2. OBJECTIVES: To evaluate and describe the anti-herpesvirus effect of ASP2151, amenamevir, a novel non-nucleoside oxadiazolylphenyl-containing herpesvirus helicase-primase complex inhibitor.20534624
F18F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM)F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication.22037848
6-(tert-butyl)-4-phenyl-4-(trifluoromethyl)-1H,3H-1,3,5-triazin-2-oneIn in vitro assays, HIV-1 reverse transcriptase (RT) activity was inhibited by compound 1 with an EC50 of 4.3 micromA Triazinone Derivative Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity. A novel HIV-1 inhibitor, 6-(tert-butyl)-4-phenyl-4-(trifluoromethyl)-1H,3H-1,3,5-triazin-2-one (compound 1), was identified from a compound library screened for the ability to inhibit HIV-1 replication.27634404
GW678248 is a novel benzophenonePreclinical assessment of GW678248 indicates that this compound potently inhibits wild-type (WT) and mutant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in biochemical assays, with 50% inhibitory concentrations (IC(50)s) between 0.8 and 6.8 nM.Cytotoxicity studies with GW678248 indicate that the 50% cytotoxicity concentration is greater than the level of compound solubility and provides a selectivity index of >2,500-fold for WT, Y181C, or K103N HIV-1.Antiviral activity of GW678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. The compound GW678248 is a novel benzophenone nonnucleoside reverse transcriptase inhibitor (NNRTI).16189079
UK-201844UK-201844 exhibited antiviral activity against HIV-1 NL4-3 in MT-2 and PM1 cells, with 50% effective concentrations of 1.3 and 2.7 microM, respectively, but did not exhibit measurable antiviral activity against the closely related HIV-1 IIIB laboratory strain.Identification and characterization of UK-201844, a novel inhibitor that interferes with human immunodeficiency virus type 1 gp160 processing.17646410
3-fluoro-2-(phosphonomethoxy)propyl (FPMP) {(S)-FPMPA amidate}Activity against hepatitis B virus (HBV) and varicella-zoster virus (VZV)The derivatization of the phosphonic acid functionality of FPMPs with a diamyl aspartate phenoxyamidate group led to a novel generation of compounds that not only demonstrate drastically improved antiretroviral potency but also are characterized by an expanded spectrum of activity that also covers hepatitis B and herpes viruses.28682067
Enviroxime-like compound, AN-12-H5Anti-enterovirusThese results suggest that AN-12-H5 is a bifunctional anti-enterovirus compound that belongs to a novel class of enviroxime-like compounds and targets both a replication step and an early stage of EV71 infection.20660150
RO-7Inhibited influenza A viruses (seasonal and 2009 pandemic H1N1 and seasonal H3N2) and B viruses (Yamagata and Victoria lineages), zoonotic viruses (H5N1, H7N9, and H9N2), and NAI-resistant variantsA Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro. Here, we characterized a novel compound, RO-7, identified as a putative PA endonuclease inhibitor.27381402
BIT225BIT225, blocks Vpu ion channel activity and also shows anti-HIV-1 activity, with a 50% effective concentration of 2.25+/-0.23 microM (mean+/-the standard error)minimal in vitro toxicity (50% toxic concentration, 284 microM) in infected MDM, resulting in a selectivity index of 126Antiviral efficacy of the novel compound BIT225 against HIV-1 release from human macrophages.19995924
4-Oxo-4,7-dihydrothieno[2,3-b]pyridinesInhibitors of human cytomegalovirus and related herpesvirus polymerases4-Oxo-4,7-dihydrothieno[2,3-b]pyridines as non-nucleoside inhibitors of human cytomegalovirus and related herpesvirus polymerases. A novel series of 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV).16134946
4-(5-(2,6-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-2-oxo-N-(2-oxopyrrolidin-1-yl)but-3-enamideExhibits low nM antiviral activity against a diverse set of HIV-1 isolates, and against HIV-2 and the simian immunodeficiency virus (SIV).A novel anti-HIV active integrase inhibitor with a favorable in vitro cytochrome P450 and uridine 5'-diphospho-glucuronosyltransferase metabolism profile.23602851
Bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065Active against wide spectrum of HIV isolatesA novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC(50)], 0.0002 to 0.0005 microM) with minimal cytotoxicity (50% cytotoxicity, 35.7 microM in CD4(+) MT-2 cells).17371811
compound 7f (A-98881)HIV-1 protease inhibition assay and the in vitro MT-4 cell culture assay (Ki = approximately 5 pM and EC50 = 0.002 microM).A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease. The design, synthesis, and molecular modeling studies of a novel series of azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV-1) protease that incorporate different ligands for the S1', S2, and S2' substrate-binding sites of HIV-1 protease are described.8558507
Benzophenone derivativesinhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells.Benzophenone derivatives: a novel series of potent and selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase. A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells.7538590
Nonpeptidic macrocyclic HIV protease inhibitorsExerted potent activity against multidrug-resistant HIV-1 variantsDesign, synthesis, protein-ligand X-ray structure, and biological evaluation of a series of novel macrocyclic human immunodeficiency virus-1 protease inhibitors to combat drug resistance. The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants.19746963
DihydroxythiophenesHIV-1Dihydroxythiophenes are novel potent inhibitors of human immunodeficiency virus integrase with a diketo acid-like pharmacophore. We have identified dihydroxythiophenes (DHT) as a novel series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors with broad antiviral activities against different HIV isolates in vitro.16809294
ABT-378Human immunodeficiency virus type 1 (HIV-1) protease inhibitorIn vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. ABT-378, a new human immunodeficiency virus type 1 (HIV-1) protease inhibitor which is significantly more active than ritonavir in cell culture, is currently under investigation for the treatment of AIDS.9696850
2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs)Anti-HIV-1Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as human immunodeficiency virus type 1 integrase inhibitors. We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs).24793360
8-substituted dipyridodiazepinoneActivity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virusNovel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors. A series of novel 8-substituted dipyridodiazepinone-based inhibitors were investigated for their antiviral activity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virus.16107158
UIC-94017 (containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere)Activity against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), approximately 0.009 micro M)minimal cytotoxicity (50% cytotoxic concentration for CD4(+) MT-2 cells, 74 micro M)Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), approximately 0.009 micro M) with minimal cytotoxicity (50% cytotoxic concentration for CD4(+) MT-2 cells, 74 micro M).14506019
Novel pyridine oxide derivatives(HIV-1) and HIV-2 strainsNovel human immunodeficiency virus (HIV) inhibitors that have a dual mode of anti-HIV action. We have found that novel pyridine oxide derivatives are inhibitors of a wide range of human immunodeficiency virus (HIV) type 1 (HIV-1) and HIV-2 strains in CEM cell cultures.14506017
Stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate) (stampidine [STAMP]), a novel aryl phosphate derivative of stavudineHIV-1We report the antiretroviral activity of stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate) (stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, against primary clinical human immunodeficiency virus type 1 (HIV-1) isolates.12384373
Pyrido [1,2a] indole derivativesInhibitory effect against purified HIV-1 reverse transcriptase (RT) in an in vitro assayPyrido [1,2a] indole derivatives identified as novel non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus type 1. Pyrido [1,2a] indole derivatives were identified as potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication during a random screening programme.10335402
1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimida zole (35)an IC50 = 200 nM against HIV-1 WT RT in an in vitro enzyme assaySynthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-Aryl-substituted benzimidazoles. The development of new nonnucleoside inhibitors of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) active against the drug-induced mutations in RT continues to be a very important goal of AIDS research.9435891
MK-4965MK-4965 is also highly potent against the WT virus and two most prevalent NNRTI-resistant viruses (viruses that harbor the K103N or the Y181C mutation), against which it had 95% effective concentrations (EC(95)s) of <30 nM in the presence of 10% fetal bovine serum. The antiviral EC(95) of MK-4965 was reduced approximately four- to sixfold when it was tested in 50% human serum.Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are the mainstays of therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections.19289522
TMC310911TMC310911 has potent activity against wild-type (WT) HIV-1 (median 50% effective concentration [EC(50)], 14 nM) and a wide spectrum of recombinant HIV-1 clinical isolates, including multiple-PI-resistant strains with decreased susceptibility to currently approved PIs (fold change [FC] in EC(50), >10).TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. TMC310911 is a novel human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) structurally closely related to darunavir (DRV) but with improved virological characteristics.21896904
GRL-04810 and GRL-05010, containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, bis-tetrahydrofuranylurethane (bis-THF), and a difluoride moietyActive against the laboratory strain HIV-1LAI (50% effective concentrations [EC50s], 0.0008 and 0.003 microM, respectively)GRL-04810 and GRL-05010 have minimal cytotoxicity (50% cytotoxic concentrations [CC50s], 17.5 and 37.0 microM, respectivelyGRL-04810 and GRL-05010, difluoride-containing nonpeptidic HIV-1 protease inhibitors (PIs) that inhibit the replication of multi-PI-resistant HIV-1 in vitro and possess favorable lipophilicity that may allow blood-brain barrier penetration.24080647
GRL008 and DRV[EC50s], 0.029 and 0.002 microM, respectively) against a multidrug-resistant clinical isolate of HIV-1 (HIVA02)A conserved hydrogen-bonding network of P2 bis-tetrahydrofuran-containing HIV-1 protease inhibitors (PIs) with a protease active-site amino acid backbone aids in their activity against PI-resistant HIV.24752271
Thiothymidine derivatives, KAY-2-41 and KAH-39-149Active against herpes simplex virus, varicella-zoster virus (VZV), and particularly against Epstein-Barr virusAntiherpesvirus activities of two novel 4'-thiothymidine derivatives, KAY-2-41 and KAH-39-149, are dependent on viral and cellular thymidine kinases. The emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients.24820089
A-790742(HIV-1) protease inhibitor, with 50% effective concentrations ranging from 2 to 7 nM against wild-type HIV-1Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742 is a potent human immunodeficiency virus type 1 (HIV-1) protease inhibitor, with 50% effective concentrations ranging from 2 to 7 nM against wild-type HIV-1.18212102
Compounds derived from scaffolds containing a thiazole replacement of the exocyclic amide with modification at position 7 and/or 9 of the bicyclic pyrimidinone coreHIV integrase inhibitorsDiscovery of potent HIV integrase inhibitors active against raltegravir resistant viruses. A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported.20685117
AIC292, diarylpyrazole-[imidazolidinone]-carboxamidesHIV-1In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.23959304
ACH-806 (GS-9132)Inhibits hepatitis C virus (HCV) replicationSelection of replicon variants resistant to ACH-806, a novel hepatitis C virus inhibitor with no cross-resistance to NS3 protease and NS5B polymerase inhibitors. We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells.18411324
C3-substituted cyclopentyltetrahydrofuranyl (Cp-THF)HIV-1 protease inhibitorsSubstituent effects on P2-cyclopentyltetrahydrofuranyl urethanes: design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors. The design, synthesis, and biological evaluation of novel C3-substituted cyclopentyltetrahydrofuranyl (Cp-THF)-derived HIV-1 protease inhibitors are described.22364812
DexlansoprazoleHuman immunodeficiency virus (HIV)-1 integrase (IN) inhibitorA novel assay for screening inhibitors targeting HIV-1 integrase dimerization based on Ni-NTA magnetic agarose beads. Human immunodeficiency virus (HIV)-1 integrase (IN), which mediates integration of viral cDNA into the cellular chromosome, is a validated antiviral drug target.27137477
Combination of boceprevir with a nucleoside analog or a non-nucleoside HCV NS5B polymerase inhibitorEffective against hepatitis C virus (HCV)A novel HCV NS3 protease mutation selected by combination treatment of the protease inhibitor boceprevir and NS5B polymerase inhibitors. Boceprevir (SCH 503034) is an orally active novel inhibitor of the hepatitis C virus (HCV) NS3 protease currently in clinical development for the treatment of hepatitis C.19747948
EI-1, HCV pseudoparticles (HCVpp)Agianst hepatitis C virus (HCV)A novel small molecule inhibitor of hepatitis C virus entry. Small molecule inhibitors of hepatitis C virus (HCV) are being developed to complement or replace treatments with pegylated interferons and ribavirin, which have poor response rates and significant side effects.20838466
5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP)The 50% effective concentration (EC50) for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect formation was 0.04 +/- 0.01 microMA novel, highly selective inhibitor of pestivirus replication that targets the viral RNA-dependent RNA polymerase. We report on the highly potent and selective antipestivirus activity of 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP).16352539
R165481 and R221239Inhibit wild-type HIV-1 RT and drug-resistant variants, including Tyr181Cys and Lys103Asn RTAn acrylonitrile substituent on R165481 substantially improves the activity of the compound against wild-type RT (and several mutants) and provides a way to generate novel inhibitors that could interact with conserved elements of HIV-1 RT at the polymerase catalytic site.16302798
NS3/4A proteinase inhibitors screened from Developmental Therapeutics Program (NCI/NIH)Hepatitis C virus (HCV)As a result, we identified several novel, previously uncharacterized, nanomolar range inhibitory scaffolds, which suppressed of the NS3/4A activity in vitro and replication of a sub-genomic HCV RNA replicon with a luciferase reporter in human hepatocarcinoma cells.22768327
Sodium (+)-isolaricireinol-2 alpha-sulfate, sodium 3,4-dihydroxy-5-methoxybenzoic acid methyl ester-4-sulfate, sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3S-sulfonate, and 3-methoxytyramine-betaxanthinActivity against H1N1 influenza virusesBased on virtual screening, MD simulation, and interaction energy evaluation, TCM candidates demonstrate good potential as novel H1 inhibitors.22012120
methyl ((S)-1-((S)-2-(4-(4-(6-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)quinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateActivity against hepatitis C virus (HCV)By varying the biphenyl-imidazole unit of daclatasvir, novel inhibitors of HCV NS5A were identified with an improved resistance profile against mutant strains of the virus while retaining the picomolar potency of daclatasvir.24729513
GS-5885Hepatitis C virus (HCV) NS5A inhibitorCharacterization of Hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885. GS-5885 is a novel hepatitis C virus (HCV) NS5A inhibitor.23877691
3'-Azidothymidine (AZT)HIVClicking 3'-azidothymidine into novel potent inhibitors of human immunodeficiency virus. 3'-Azidothymidine (AZT) was the first approved antiviral for the treatment of human immunodeficiency virus (HIV).24102161
Cationic N,N-Dimethyl[70]fulleropyrrolidinium Iodide DerivativesAnti-HIV-1Collectively, our studies indicate fullerene derivatives 2a-c as potent and novel HIV-1 maturation inhibitors.28002960
EMT-305 and EMT-104Activity against Influenza A virusComputational and experimental screening of extensive and water soluble compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without detectable toxic effects on host cells.28713784
Inhibitors designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands.HIV-1 protease inhibitorDesign and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated.17696512
3,5-diamino-N-aryl-1H-pyrazole-4-carbothioamide and 4-amino-5-benzoyl-N-phenyl-2-(substituted-amino)-1H-pyrrole-3-carbothioamide derivativesAnti-HIV-1Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions.28859311
Triazolo-pyrimidine derivativesInhibitors of hepatitis B virus surface antigen (HBsAg) secretionDesign, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies.21786803
Osalmid and its derivative 4-cyclopropyl-2-fluoro-N-(4-hydroxyphenyl) benzamide (YZ51)HBVFurthermore, 4-cyclopropyl-2-fluoro-N-(4-hydroxyphenyl) benzamide (YZ51), a novel derivative of osalmid, showed higher efficacy than osalmid with more potent RR inhibitory activity.26774458
GRL-0519, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing tris-tetrahydrofuranylurethane (tris-THF) and a sulfonamide isostereActivity against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0005 to 0.0007 microM)minimal cytotoxicity (50% cytotoxic concentration [CC50], 44.6 microM)GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 variants in vitroWe report that GRL-0519, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing tris-tetrahydrofuranylurethane (tris-THF) and a sulfonamide isostere, is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0005 to 0.0007 microM) with minimal cytotoxicity (50% cytotoxic concentration [CC50], 44.6 microM).23403426
Novel inhibitors of RSV including the P13 fusion inhibitor, and the PG545 virucideRespiratory syncytial virus (RSV)Here we describe the cell culture-based methods used in our laboratory in identification of novel inhibitors of RSV including the P13 fusion inhibitor, and the PG545 virucide.23821281
FA-583 and FA-617Influenza A VirusHere we identify and characterize two structurally different novel fusion inhibitors of the influenza A virus group 1 hemagglutinin (HA), FA-583 and FA-617, with low nanomolar activities.26676787
cpd 1, 2, and 3Respiratory Syncytial Virus (RSV)Here we report the characterization of three novel classes of RSV replication inhibitors identified through a high throughput RSV replicon screen of ?1million compounds in the AstraZeneca compound collection.25542974
GRL-142, containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuranPotent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrationsHere, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration.29039736
4'-C-cyano-2-amino-2'-deoxyadenosine (CAdA)Activity against hepatitis B virus (HBV), half maximal inhibitory concentration [IC50 ] = 0.4 nM) and HIV-1 (IC50 = 0.4 nM4'-modified nucleoside analogs: potent inhibitors active against entecavir-resistant hepatitis B virus26122273
GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate)GLS4 demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50 value of 1nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50 values in the range of 10-20nMHerein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyri midine-5-carboxylate) which is now in clinical phase 2.28082068
Pyridone-based compound PF-46396Anti-HIV-1HIV-1 maturation inhibitors are novel as they target the Gag protein, specifically by inhibiting CA-SP1 proteolytic cleavage.27384665
Cytidine analogue D-d4FC (DPC817, Reverset)Anti-HIV-1HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (Reverset). Nucleoside reverse transcriptase inhibitors (NRTIs) represent the cornerstone of highly active antiretroviral therapy when combined with non-nucleoside reverse transcriptase inhibitors (NNRTIs) or HIV-1 protease inhibitors (PIs).12790516
Three-ring oxadiazole compoundsAnti-HIV-1Identification of novel bifunctional HIV-1 reverse transcriptase inhibitors. The increasing prevalence of mutations in HIV-1 reverse transcriptase (RT) that confer resistance to existing NRTIs and NNRTIs underscores the need to develop RT inhibitors with novel mode-of-inhibition and distinct resistance profiles.29029095
A series of 1,3,5-triazine compoundsAnti-HCVImportantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection.22545104
D4GTP (the planar 2',3'-unsaturated deoxyribose guanosine analogue that is complementary to D4TTP)Anti-HIV-1In contrast to CBVTP, D4GTP was found to be an excellent substrate for RT(WT) and no resistance was conferred by the M184V mutation, thus providing novel insight into structure-activity relationships for nucleoside-based inhibitors.11955063
Bromocriptine (BRC)Dengue virus (DENV) half maximal effective concentration [EC50], 0.8-1.6 microMHalf maximal cytotoxicity concentration [CC50], 53.6 microM)In summary, BRC was found to be a novel DENV inhibitor and a potential candidate for the treatment of DENV infectious disease.27181378
2,2'-diselenobisbenzamides (DISeBAs)Anti-HIVIn this manuscript, we have identified a series of 2,2'-diselenobisbenzamides (DISeBAs) as novel HIV retroviral nucleocapsid protein 7 (NCp7) inhibitors.26613134
VRX-329747 and VRX-413638Anti-HIV-1In this study, we report a novel series of nonnucleoside inhibitors of HIV-1, exemplified by VRX-329747 and VRX-413638, which inhibit both NNRTI- and NRTI-resistant HIV-1 isolates.16870771
GSK2485852 (referred to here as GSK5852)Hepatitis C virus (HCV) NS5B polymerase inhibitor with 50% effective concentrations (EC50s)In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. GSK2485852 (referred to here as GSK5852) is a hepatitis C virus (HCV) NS5B polymerase inhibitor with 50% effective concentrations (EC50s) in the low nanomolar range in the genotype 1 and 2 subgenomic replicon system as well as the infectious HCV cell culture system.23939896
3-hydroxypyrimidine-2,4-dionesActivity against human immunodeficiency virus (HIV)Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (INIs).21381765
JTK-853hepatitis C virus (HCV)JTK-853, a novel non-nucleoside hepatitis C virus polymerase inhibitor, demonstrates a high genetic barrier to resistance in vitro. JTK-853 is a novel, non-nucleoside, palm site-binding hepatitis C virus (HCV) polymerase inhibitor that has demonstrated antiviral activity in HCV-infected patients during 3 days of treatment.24008863
1, 4-dihydro-2H-3, 1-benzoxazin-2-onesThe compound was a potent inhibitor of the wild-type HIV-1 RT (Ki = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture.L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant viral variants.8592986
2-Hydroxyisoquinoline-1,3(2H,4H)-dioneAnti-HIV-1Magnesium chelating 2-hydroxyisoquinoline-1,3(2H,4H)-diones, as inhibitors of HIV-1 integrase and/or the HIV-1 reverse transcriptase ribonuclease H domain: discovery of a novel selective inhibitor of the ribonuclease H function. 2-Hydroxyisoquinoline-1,3(2H,4H)-dione was recently discovered as a scaffold for the inhibition of HIV-1 integrase and the ribonuclease H function of HIV-1 reverse transcriptase.21366258
ArtocarpinH1N1 IC(50) values, determined in chemiluminescence-based NA inhibition assays, are in the range of 0.18-17 microMIn particular, artocarpin exhibits high affinity toward three H1N1 oseltamivir-sensitive influenza A viruses. It also inhibits the NA of an oseltamivir-resistant H1N1 isolate.21452980
Sifuvirtide (SFT)Anti-HIVOur data present important information for developing SFT for clinical use and for designing novel HIV fusion inhibitors.22228771
Protease inhibitors (PI's) bearing 1,3,4-oxadiazoles at the P1' positionAnti-HIV-1P1' oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1. HIV-1 protease inhibitors (PI's) bearing 1,3,4-oxadiazoles at the P1' position were prepared by a novel method involving the diastereoselective installation of a carboxylic acid and conversion to the P1' heterocycle.15324882
BPR0Z-194, one of the pyridyl imidazolidinonesEnterovirus 71Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor.15328120
RSV604, a novel benzodiazepineRespiratory syncytial virus (RSV)RSV604, a novel inhibitor of respiratory syncytial virus replication. Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, ye+B11t no effective vaccine or antiviral treatment is available.17576833
GSK2248761[EC(50)] = 36.9 ng/ml) against HIV-1Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains.22314532
A series of novel N-alkoxy-arylsulfonamideHIV protease inhibitorsSynthesis and antiviral activities of novel N-alkoxy-arylsulfonamide-based HIV protease inhibitors. A series of novel N-alkoxy-arylsulfonamide HIV protease inhibitors with low picomolar enzyme activity and single digit nanomolar antiviral activity is disclosed. DOI: 10.1016/j.bmcl.2005.05.10115975788
3-aryl-phospho-indole (API)Anti-HIV-1Synthesis and biological evaluation of aryl-phospho-indole as novel HIV-1 non-nucleoside reverse transcriptase inhibitors. A novel series of 3-aryl-phospho-indole (API) non-nucleoside reverse transcriptase inhibitors of HIV-1 was developed.21142105
Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI)Anti-HIV-1The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resistant viral strains. Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains.12852969
BicyclamsHuman immunodeficiency virus type 1 (HIV-1) and HIV-2 inhibitorThe molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. Bicyclams are a novel class of antiviral compounds which act as potent and selective inhibitors of the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2.8551604
CP32MInhibit a large panel of diverse HIV-1 variants, including subtype B', CRF07_BC, and CRF01_AE recombinants and naturally occurring or induced T20-resistant viruses.Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use.22679024
AZ-27Respiratory syncytial virus (RSV) inhibitorsThis novel and broad-spectrum RSV L polymerase inhibitor may pave the way toward an efficacious RSV therapeutic and provide a new tool for interrogation of the L protein function.24777090
Alkyl Amine Bevirimat DerivativesAnti-HIV-1To overcome the loss of BVM activity induced by polymorphisms in SP1, we carried out an extensive medicinal chemistry campaign to develop novel maturation inhibitors.26482309
Protease inhibitor SG85enterovirus 71 (EV71)We demonstrate that the novel enteroviral protease inhibitor (PI) SG85 and capsid binder (CB) vapendavir efficiently inhibit the in vitro replication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C.25199773
Bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine]Inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta)We describe a novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine], which inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta).7685995
ABT-450Inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively.In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450. The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively.25451053
GLS4The IC(50) of GLS4 was 0.012 microM, which is significantly lower than that of lamivudine (0.325 microM).CONCLUSIONS: GLS4 is a new and unique potential anti-HBV agent that possesses a different mechanism of action than existing therapeutic drugs.22668794
2-phenylbenzimidazole derivativesSelectively and potently active against the bovine viral diarrhea virus (BVDV)Pharmacophore modeling, resistant mutant isolation, docking, and MM-PBSA analysis: Combined experimental/computer-assisted approaches to identify new inhibitors of the bovine viral diarrhea virus (BVDV). Starting from a series of our new 2-phenylbenzimidazole derivatives, shown to be selectively and potently active against the bovine viral diarrhea virus (BVDV), we developed a hierarchical combined experimental/molecular modeling strategy to explore the drug leads for the BVDV RNA-dependent RNA-polymerase.20189812
Arylazoenamine derivativesSelectively and potently active against the bovine viral diarrhea virus (BVDV), we developed a hierarchical combined experimental/molecular modeling strategy to explore the drug leads for the BVDV RNA-dependent RNA polymerase.Synergistic experimental/computational studies on arylazoenamine derivatives that target the bovine viral diarrhea virus RNA-dependent RNA polymerase. Starting from a series of arylazoenamine derivatives, shown to be selectively and potently active against the bovine viral diarrhea virus (BVDV), we developed a hierarchical combined experimental/molecular modeling strategy to explore the drug leads for the BVDV RNA-dependent RNA polymerase.20638852
Compound 27, piperidine-substituted thiophene[3,2-d]pyrimidine scaffoldCompound 27 was the most potent; compared with ETV, its antiviral efficacy was 3-fold greater against WT, 5-7-fold greater against Y181C, Y188L, E138K, and F227L+V106A, and nearly equipotent against L100I and K103N, though somewhat weaker against K103N+Y181C.27 has lower cytotoxicity (CC50 > 227 microM) and a huge selectivity index (SI) value (ratio of CC50/EC50) of >159101We designed and synthesized a series of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a piperidine-substituted thiophene[3,2-d]pyrimidine scaffold, employing a strategy of structure-based molecular hybridization and substituent decorating.27541578
Remazol Brilliant Blue RRemazol Brilliant Blue R (RB19, an anthraquinone dye), which inhibited WT NA and MDR NA with IC(50) values of 3.4 and 4.5 microM, respectively.Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye), which inhibited WT NA and MDR NA with IC(50) values of 3.4 and 4.5 microM, respectively.23437217
Macrocyclic acylsulfonamidePotent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants.This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants.23271737
Chebulagic acid (CHLA) and punicalagin (PUG)Could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection.inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells.Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection.21307190
Nonnucleoside reverse transcriptase inhibitor (NNRTI) UC78125 microM UC781 provided essentially equivalent microbicidal activity against NNRTI-resistant and wt virusIn vitro microbicidal activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant human immunodeficiency virus type 1. The nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 is under development as a microbicide to prevent sexual transmission of the human immunodeficiency virus type 1 (HIV-1).16611904
Stilbene 1,2-diaminesCompounds selectively block the initiation of replication of incoming HCV RNA but have no impact on viral entry, primary translation, or ongoing HCV RNA replication, nor do they suppress persistent HCV infection.prevent HCV infection at nontoxic, low micromolar concentrations in cell culture.Using a cell-based colorimetric screening assay to interrogate a 1,200-compound chemical library for anti-HCV activity, we identified a family of 1,2-diamines derived from trans-stilbene oxide that prevent HCV infection at nontoxic, low micromolar concentrations in cell culture.21430055
Distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2-carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC 651016)NSC 651016 inhibited in vitro replication of a wide range of HIV-1 isolates, as well as HIV-2 and SIV, and exhibited in vivo anti-HIV-1 activity in a murine model.NSC 651016 represents an attractive candidate for the chemotherapeutic treatment of HIV-1 infection and as a microbicide to prevent the sexual transmisssion of HIV-1.9632350
D- and L-(beta)-deoxy- and -dideoxynucleoside triphosphate analoguesL-(beta)-enantiomers of nucleoside RT inhibitors were synergistic when combined with nonnucleoside RT inhibitorsPotentiation of inhibition of wild-type and mutant human immunodeficiency virus type 1 reverse transcriptases by combinations of nonnucleoside inhibitors and d- and L-(beta)-dideoxynucleoside triphosphate analogs. Combinations of reverse transcriptase (RT) inhibitors are currently used in anti-human immunodeficiency virus therapy in order to prevent or delay the emergence of resistant virus and to improve the efficacy against viral enzymes carrying resistance mutations.11257034
N-Butyldeoxynojirimycin (NB-DNJ)When encapsulated inside liposomes, NB-DNJ inhibited HIV-1 with final concentrations in the nmol/l range (IC50 = 4 nmol/l), a 100 000-fold enhancement in IC50 relative to free NB-DNJ.N-Butyldeoxynojirimycin is a broadly effective anti-HIV therapy significantly enhanced by targeted liposome delivery. NB-DNJ CD4 liposomes demonstrated additional antiviral effects, reducing viral secretion by 81% and effectively neutralizing free viral particles to prevent further infections.18753929
CDG (carbocyclic 2'-deoxyguanosine) and abacavir ([1S,4R]-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol)Drug assays indicated that the lamivudine-resistant virus exhibited reduced sensitivity to penciclovir [9-(4-hydroxy-3-hydroxymethyl-but-1-yl) guanine] but was still inhibited by the nucleoside analogues CDG (carbocyclic 2'-deoxyguanosine) and abacavir ([1S,4R]-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol).Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening. Lamivudine [beta-L-(-)-2',3'-dideoxy-3'-thiacytidine] is a potent inhibitor of hepadnavirus replication and is used both to treat chronic hepatitis B virus (HBV) infections and to prevent reinfection of transplanted livers.12760870
Boceprevir-S isomer (SCH 534128)Median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL.Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir. Copyright ? 2014 European Society of Clinical Microbiology and Infectious Diseases.25658567
4-oxo-4H-1-benzopyran-8-carbaldehydes 11a-11gMost promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent.A series of novel isoflavonoids were synthesized based on structural modifications of daidzein, an active ingredient of traditional Chinese medicine (TCM) and evaluated for their anti-influenza activity, in vitro, against H1N1 Tamiflu-resistant (H1N1 TR) virus in the MDCK cell line. Among them, 4-oxo-4H-1-benzopyran-8-carbaldehydes 11a-11g were most promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent. 3-(4-Bromophenyl)-7-hydroxy-4-oxo-4H-1-benzopyran-8-carboxaldehyde (11c) displayed the best inhibitory activity (EC50 , 29.0 microM) and selectivity index (SI>10.3).25879510
Carraguard-based formulationPC-817 appeared no more effective than Carraguard in vivo, due to the limited activity of a single dose of MIV-150 and the dominant barrier effect of Carraguard.Efficacy of Carraguard-based microbicides in vivo despite variable in vitro activity. Anti-HIV microbicides are being investigated in clinical trials and understanding how promising strategies work, coincident with demonstrating efficacy in vivo, is central to advancing new generation microbicides.18776937
4'-methoxyflavone and 2'-hydroxy-4-methoxychalconeIn-silico study, binders of the 150-cavity of neuraminidase (NA)A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1.27412704
Diphenyl etherNon-nucleoside reverse transcriptase inhibitors with excellent potency against resistant mutant viruses and promising pharmacokinetic propertiesDiphenyl ether non-nucleoside reverse transcriptase inhibitors with excellent potency against resistant mutant viruses and promising pharmacokinetic properties. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are part of the preferred treatment regimens for individuals infected with HIV.19006142
Indolylarylsulfones (IASs), halo- and nitro-substituted IAS derivativesExhibited high selectivity to the mutant RT in complex with its substrates, behaving as uncompetitive inhibitors.Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. BACKGROUND: Novel indolylarylsulfones (IASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT).22095519
Icosahedral metallacarboranesPotent and specific competitive inhibitors of drug-resistant HIV PRs prepared either by site-directed mutagenesis or cloned from HIV-positive patients.Inorganic polyhedral metallacarborane inhibitors of HIV protease: a new approach to overcoming antiviral resistance. HIV protease (PR) is a prime target for rational anti-HIV drug design.18598016
Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol)Active against ganciclovir- and foscarnet-resistant human cytomegalovirus UL97 mutantsThe Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol) were previously shown to be potent inhibitors of AD169 and Towne HCMV reference strains and postulated to share a common phosphorylation pathway with ganciclovir (GCV) possibly involving the UL97-encoded phosphotransferase.12406510
R1626 plus peginterferon Alfa-2aPotent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirinR1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin. R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study.18570306
Benzothiadiazine-substituted tetramic acidsPotent inhibitors of the hepatitis C virus RNA-dependent RNA polymeraseAn efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted tetramic acids: potent inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. An efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted tetramic acids is reported.16455253
KNI-227 and KNI-272the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively.The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI-272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells.In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains.8494379
2'-deoxy-4'-C-ethynyl-2-fluoroadenosine and 2'-deoxy-4'-C-ethynyl-2-chloroadenosineHave supremely high activity against all human immunodeficiency viruses including multidrug-resistant HIV and low toxicity.low toxicity.Development of modified nucleosides that have supremely high anti-HIV activity and low toxicity and prevent the emergence of resistant HIV mutants. An idea to use 4'-C-substituted-2'-deoxynucleoside derivatives was proposed based on a working hypothesis to solve the problems of existing acquired immune deficiency syndrome chemotherapy (highly active antiretroviral therapy).21422739
GRL-1388 and -1398GRL-1388 was as potent as darunavir (DRV) against various drug-resistant HIV-1 laboratory strains with 50% effective concentration (EC(50)s) of 2.6 to 32.6 nM. GRL-1398 was significantly more potent against such variants than DRV with EC(50)s of 0.1 to 5.7 nM. GRL-1388 and -1398 were also potent against multiple-PI-resistant clinical HIV-1 variants ((CL)HIV-1(MDR)) with EC(50)s ranging from 2.7 to 21.3 nM and from 0.3 to 4.8 nM, respectively.Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants. We identified GRL-1388 and -1398, potent nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran (Tp-THF).21282450
MK-1439Treatment of HIV infection.Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.24412110
GRL-5010A and GRL-4410AMore effective than darunavir in inhibiting mature PR20 and show promise for further development of antiviral agents targeting highly resistant PR mutants.Substituted Bis-THF Protease Inhibitors with Improved Potency against Highly Resistant Mature HIV-1 Protease PR20. An extremely drug resistant mutant of HIV-1 protease (PR) bearing 20 mutations (PR20) has been studied with two potent antiviral investigational inhibitors.26010498
TMC647055 (TMC)A novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase.TMC647055 (TMC) is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase. However, mutations that result in drug resistance to TMC have been reported.26836778
EDP-239Hepatitis C Virus NS5A InhibitorEDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo27503644
Three amide-DAANs 8e, 4a, and 4bHigh potency against wild-type and rilpivirine-resistant viral strains and multiple desirable drug-like properties.Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus.28465101
TMC125-R165335 (etravirine)TMC125-R165335 and related anti-AIDS drug candidates can bind the enzyme RT in multiple conformations and thereby escape the effects of drug-resistance mutations.Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. Anti-AIDS drug candidate and non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in viral load similar to that observed with a five-drug combination in na?ve patients and retains potency in patients infected with NNRTI-resistant HIV-1 variants.15115397
7-Deaza-2'-C-methyl-adenosinePotent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic propertiesA 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties. Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options.15388457
Aurintricarboxylic acidPotent inhibitor of influenza A and B virus neuraminidasesAurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases. BACKGROUND: Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively.20020057
2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236)PHI-236 displayed high-binding affinity (Ludi K(i) = 0.07 microM) for HIV-1 RT and robust anti-HIV activity against the wild type (IC50 = <0.001 microM) as well as primary clinical isolates (IC50 = 0.009-0.04 microM) carrying multiple RT gene mutations associated with NRTI and NNRTI resistance.Discovery of 2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236) as a potent broad-spectrum anti-human immunodeficiency virus microbicide.16254003
beta-L-2',3'-Dideoxycytidine (beta-L-ddC) and beta-L-5-fluoro-2',3'-dideoxycytidine (5-F-beta-L-ddC)The beta-L-dideoxycytidine nucleosides had similar anti-HIV-1 activities, significantly greater anti-HBV activitiesdecreased toxicities to a B-cell line, T-cell lines, and human bone marrow progenitor cells.Influence of stereochemistry on antiviral activities and resistance profiles of dideoxycytidine nucleosides. beta-L-2',3'-Dideoxycytidine (beta-L-ddC) and beta-L-5-fluoro-2',3'-dideoxycytidine (5-F-beta-L-ddC) were prepared and shown to have potent activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV).7518218
[tetrahydroimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine, nevirapine, pyridinone, bis(heteroaryl)piperazine, etc.]Potent inhibitors of HIV-1 replication in cell culture.Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors. The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors [tetrahydroimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine, nevirapine, pyridinone, bis(heteroaryl)piperazine, etc.] are potent inhibitors of HIV-1 replication in cell culture.7682649
N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thioureaHIV-1 inhibition assays was: HI-445 = HI-346 (IC50 = 3 nM) > MKC-442 (IC50 = 4 nM) = AZT (IC50 = 4 nM) > trovirdine (IC50 = 7 nM) > delavirdine (IC50 = 9 nM) > nevirapine (IC50 = 34 nM).N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1.10509923
MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU)The 50 and 90% effective concentrations for HIV-1 (HTLV-IIIB strain) replication in MT-4 cells were 15 and 98 nM, respectively.Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro. MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU) has recently been identified as a highly potent and specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.7518216
5-Fluorouracil, 5-fluorouridine (FUrd), 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorocytidine (FCyd), 5-fluoro-2'-deoxycytidine (FdCyd), 5-trifluoro-2'-deoxythymidine (F3dThd), and the 5'-monophosphates and 3',5'-cyclic monophosphatesActivity against thymidine kinase-deficient (TK-) herpes simplex virusPotent activity of 5-fluoro-2'-deoxyuridine and related compounds against thymidine kinase-deficient (TK-) herpes simplex virus: targeted at thymidylate synthase. Other 5-substituted 2'-deoxyuridines that have previously been recognized as potent thymidylate synthase inhibitors behaved in a similar fashion.3039343
(S,S)-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediolPotent inhibitors of rhinovirusesAntiviral activity in tissue culture systems of bis-benzimidazoles, potent inhibitors of rhinoviruses.4333892
Pyridinone derivativesPotent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and HIV-1 replication in cell culture.L-702,019 was also a potent inhibitor of the replication of mutant HIV-1 containing the individual mutations at amino acid 103 or 181 as well as of clinical isolates resistant to L-697,661 and L-696,229.7685996
PNU-140690 (sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrone)A potent, nonpeptidic inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease currently under clinical evaluation.In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates. PNU-140690 (sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrone) is a potent, nonpeptidic inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease currently under clinical evaluation.9371335
(-)-beta-D-2, 6-diaminopurine-dioxolaneSuppressive effects of the K65R and L74V mutations on AZT resistance.In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. Human immunodeficiency virus type 1 (HIV-1) isolates resistant to (-)-beta-D-dioxolane-guanosine (DXG), a potent and selective nucleoside analog HIV-1 reverse transcriptase (RT) inhibitor, were selected by serial passage of HIV-1(LAI) in increasing drug concentrations (maximum concentration, 30 microM). Two independent selection experiments were performed.10858331
2',3'-dideoxy-3'-thiacytidine (3TC)A potent inhibitor of wild-type human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT).Wild-type and YMDD mutant murine leukemia virus reverse transcriptases are resistant to 2',3'-dideoxy-3'-thiacytidine. The antiretroviral nucleoside analog 2',3'-dideoxy-3'-thiacytidine (3TC) is a potent inhibitor of wild-type human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT).10864683
L-chicoric acidA potent and selective inhibitor of HIV-1 integrase that also inhibits HIV-1 replication in cell culture.L-chicoric acid is a potent and selective inhibitor of HIV-1 integrase that also inhibits HIV-1 replication in cell culture.10867160
DPC 817, 2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (PSI 5582 D-D4FC)A cytidine nucleoside analog with activity against zidovudine- and lamivudine-resistant viral variantsDPC 817, 2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (PSI 5582 D-D4FC) is a potent inhibitor of HIV type 1 replication in vitro.11959574
1263W941263W94 inhibited viral replication in a dose-dependent manner, with a mean 50% inhibitory concentration (IC(50)) of 0.12 +/- 0.01 microMPotent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. enzimidazole nucleosides have been shown to be potent inhibitors of human cytomegalovirus (HCMV) replication in vitro.12121906
Imidazole-linked pinanamine derivatives (compound 33)Inhibited the amantadine-resistant virus (IC50 = 3.4 microM) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated.Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus. We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak.26722757
Benzodithiin compound (RD3-0028)RD3-0028 inhibits RSV replication by interfering with intracellular processing of the RSV fusion protein, or a step immediately thereafter, leading to loss of infectivity.Mechanism of selective inhibition of respiratory syncytial virus by a benzodithiin compound (RD3-0028). RD3-0028, a compound with a benzodithiin structure, was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication.11529559
Methyl 3',3"-dichloro-4',4"-dimethoxy-5', 5"-bis(methoxycarbonyl)-6,6-diphenyl-5-hexenoate (ADAM II)ADAM II inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 microM but was inactive as an inhibitor of HIV-1 attachment/fusion to cells, protease, integrase, and the nucleocapsid protein.New alkenyldiarylmethanes with enhanced potencies as anti-HIV agents which act as non-nucleoside reverse transcriptase inhibitors. The most potent compound proved to be methyl 3',3"-dichloro-4',4"-dimethoxy-5', 5"-bis(methoxycarbonyl)-6,6-diphenyl-5-hexenoate (ADAM II), which displayed an EC50 of 13 nM for inhibition of the cytopathic effect of HIV-1RF in CEM-SS cells.9622549
2-fluoroadenosine analogue 322-fluoroadenosine analogue 32 showed antiviral potency as well as high cytotoxicity (IC(50) 1.5, 1.1, and 7.6 microM for PBM, CEM, and Vero, respectively) whereas no other compound showed cytotoxicity up to 100 microM.Stereoselective synthesis and antiviral activity of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. The antiviral activity of the synthesized compounds were evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells, among which cytidine 17, 5-fluorocytidine 18, adenosine 24, and 2-fluoroadenosine 32 showed moderate to potent anti-HIV activities (EC(50) 1.3, 11.6, 8.1, and 1.2 microM, respectively).12383014
Cytosine 17, 5-fluorocytosine 18, and adenine 27 derivativesShowed potent anti-HIV activities (EC(50) = 0.12, 0.15, and 1.74 microM, respectively) without significant cytotoxicity up to 100 microM in human PBM, CEM, and Vero cells.Synthesis, anti-HIV activity, and molecular mechanism of drug resistance of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides. The antiviral activity of the newly synthesized compounds was evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells, among which the cytosine 17, 5-fluorocytosine 18, and adenine 27 derivatives showed potent anti-HIV activities (EC(50) = 0.12, 0.15, and 1.74 microM, respectively) without significant cytotoxicity up to 100 microM in human PBM, CEM, and Vero cells.12540238
Diketo acid compound L-742,001Two- to 3-fold resistance was seen for the T20A, L42T, and V122T mutants, and the R124Q and Y130A mutants were 3-fold more sensitive to L-742,001.The diketo acid compound L-742,001 was previously identified as a potent inhibitor of the influenza virus endonuclease reaction, but information on its precise binding mode to PA or potential resistance profile is limited.23824822
DPC 681 and DPC 684A panel of chimeric viruses constructed from clinical samples from patients who failed PI-containing regimens and containing 5 to 11 mutations, including positions 10, 32, 46, 47, 50, 54, 63, 71, 82, 84, and 90 had mean IC(50) values of <20 nM for DPC 681 and DPC 681, respectivelyDPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants. Two compounds resulting from our studies, designated DPC 681 and DPC 684, are potent and selective inhibitors of HIV protease with IC(90)s for wild-type HIV-1 of 4 to 40 nM.11600351
N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thi ourea (HI-236)The activity of HI-236 against RT-MDR was superior to that of other anti-HIV agents tested, in the following order, from high to low activity; HI-236 (IC50 5 nM), HI-240 (IC50 6 nM), trovirdine (IC50 20 nM), zidovudine (IC50 150 nM), MKC-442 (IC50 300 nM), delavirdine (IC50 400 nM) and nevirapine (IC50 5 microM).Our lead compound, N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thi ourea (HI-236) was tested against clinically observed non-nucleoside inhibitor (NNI)-resistant mutated strains of HIV.. HI-236 was more potent than trovirdine, MKC-442 and zidovudine against the drug-sensitive HIV-1 strain IIIB, 50-100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17.10574178
Lignosulfonic acid (LA)LA demonstrated potent inhibitory activity of HIV replication against a wide range of R5 and X4 HIV strains and prevented the uptake of HIV by bystander CD4+ T cells from persistently infected T cells in vitro (IC50: 0.07 - 0.34 microM). LA also inhibited HSV-2 replication in vitro in different cell types (IC50: 0.42 - 1.1 microM) and in rodents in vivo.The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications. 26132818
4"-Benzoylureido-TSAO derivativesA stringent structure-antiviral activity relationship was observed for the 4"-benzoylureido- TSAO derivatives for which the concomitant presence of a highly lipophilic substituent at both 2'- and 5'-positions was required to fully preserve the antihuman cytomegalovirus efficacy.4"-Benzoylureido-TSAO derivatives as potent and selective non-nucleoside HCMV inhibitors.18707089
2'-deoxy-3'-oxa-4'-thiocytidine (dOTC)The mean 50% inhibitory concentration of dOTC for drug-naive isolates was 1.76 microM, rising to only 2.53 and 2.5 microM for viruses resistant to 3TC and viruses resistant to 3TC and AZT, respectively.Both 5'-triphosphate (TP) derivatives of dOTC were more potent than 3TC-TP at inhibiting HIV-1 reverse transcriptase (RT) in vitro.10428900
Pyromeconic acid and derivativesThis approach ultimately resulted in the development of a lead compound with an IC50 value of 14 nM, which displayed an EC50 value of 2.1 microM against H1N1 influenza virus in MDCK cells.Fragment-Based Identification of Influenza Endonuclease Inhibitors. Herein we report the development of inhibitors of influenza PA endonuclease derived from lead compounds identified from a metal-binding pharmacophore (MBP) library screen. Pyromeconic acid and derivatives thereof were found to be potent inhibitors of endonuclease.27291165
JM3100, bicyclam derivativeJM3100, in which the cyclam moieties are tethered by an aromatic bridge [i.e., phenylenebis(methylene)], inhibits the replication of various HIV-1 and HIV-2 strains in various cell lines at a 50% effective concentration (EC50) of 1 to 10 ng/ml, which is about 100-fold lower than the concentration required for JM2763 to inhibit HIV replication and at least 100,000-fold lower than the cytotoxic concentration (> 500 micrograms/ml).Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100. Bicyclams, in which the cyclam (1,4,8,11-tetraazacyclotetradecane) moieties are tethered via an aliphatic bridge (i.e., propylene, as in JM2763) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) (E.7913308
MRL-1237MRL-1237 inhibited poliovirus-specific RNA synthesis in HeLa cells infected with a wild strain but not with an F164Y mutant.Mutations in the 2C region of poliovirus responsible for altered sensitivity to benzimidazole derivatives. MRL-1237, [1-(4-fluorophenyl)-2-(4-imino-1,4-dihydropyridin-1-yl) methylbenzimidazole hydrochloride], is a potent and selective inhibitor of the replication of enteroviruses.10756027
AT-61, a phenylpropenamide derivative, alone and in combination with (-)beta-L-2',3'-dideoxy-3'-thiacytidineThe potency of AT-61 was not affected by one of the mutations responsible for (-)-beta-L-2', 3'-dideoxy-3' thiacytidine (3TC) resistance in HBV, and AT-61 acted synergistic with 3TC to inhibit HBV replication.AT-61 (81 microM) was not cytotoxic or antiproliferative to several cell lines and had no antiviral effect on woodchuck or duck HBV, human immunodeficiency virus type 1, herpes simplex virus type 1, vesicular stomatitis virus, or Newcastle disease virus.AT-61, a member of a novel class of phenylpropenamide derivatives, was found to be a highly selective and potent inhibitor of human hepatitis B virus (HBV) replication in four different human hepatoblastoma cell lines which support the replication of HBV (i.e., HepAD38, HepAD79, 2.2.15, and transiently transfected HepG2 cells).9835512
2-(quinolin-3-yl)acetic acid derivativesHIV-1 integrase inhibitorsWe have rationally designed a series of 2-(quinolin-3-yl)acetic acid derivatives (LEDGINs) that act as potent inhibitors of the LEDGF/p75-integrase interaction and HIV-1 replication at submicromolar concentration by blocking the integration step.20473303
Novel fluorine-containing DAPYActivities against wild-type (WT) HIV-1 and NNRTI-resistant strainsNovel fluorine-containing DAPY derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2014072419.26415039
OrganosilanesPotent antiviral activity against a panel of human clinical isolates of influenza A viruses, including viruses that are resistant to amantadine, oseltamivir, or both.Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses. In this study we report the design and synthesis of the first class of organosilanes that have potent antiviral activity against a panel of human clinical isolates of influenza A viruses, including viruses that are resistant to amantadine, oseltamivir, or both.28433777
Amino-bis-tetrahydrofuran Derivative [25f, 25i, and 25j]25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir.Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies. Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described.26306007
Benzamide derivative named AH0109Exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 microM in HIV-1-susceptible CD4(+) C8166 T cells.In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 microM in HIV-1-susceptible CD4(+) C8166 T cells.23669388
4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA)Similar to WT RT, the N348I RT is inhibited by EFdA mainly at the point of incorporation through decreased translocation.Bond Life Sciences Center and Department of Molecular Microbiology & Immunology, School of Medicine, University of Missouri, Columbia, MO 65211, USA. 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a highly potent inhibitor of HIV-1 reverse transcriptase (RT).23273211
NVP018A potent inhibitor of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows minimal inhibition of major drug transporters, and has a high barrier to generation of both HCV and HIV-1 resistanceNVP018 is a potent inhibitor of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows minimal inhibition of major drug transporters, and has a high barrier to generation of both HCV and HIV-1 resistance.25619934
5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP)The compound resulted in a dose-dependent antiviral effect in PK(15) cells with a 50% effective concentration (EC(50)) for the inhibition of CSFV Alfort(187) (subgroup 1.1) of 1.6+/-0.4 microM and for CSFV Wingene (subgroup 2.3) 0.8+/-0.2 microM.We here report that 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a highly potent inhibitor of the in vitro replication of CSFV.17997169
Phosphonoformate (foscarnet; PFA)Except for an HIV-1 variant encoding the K65R mutation in RT that exhibited 3.3- to 8.2-fold resistance, the nucleoside-resistant viruses included in the panel were sensitive to the PFA prodrugs (<3-fold increase in 50% inhibitory concentration)its use for the treatment of HIV-1 infection is limited by toxicity and the lack of an orally bioavailable formulation.Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside-resistant human immunodeficiency virus type 1 and select for resistance mutations that suppress zidovudine resistance. Phosphonoformate (foscarnet; PFA) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), but its use for the treatment of HIV-1 infection is limited by toxicity and the lack of an orally bioavailable formulation.11353603
BI-RG-58750% inhibitory concentration of 84 nM against HIV-1 reverse transcriptase activity.BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.1708976
Compounds bearing a 3-isopropyl and 3-iodine groupThe most potent inhibitors with EC50 of 4 nMNovel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs).23540737
S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC)Potent in vitro and in vivo activity against a broad range of herpesviruses, including acyclovir-resistant herpes simplex virus (HSV)Treatment with intravenous (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine of acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with AIDS.8077713
2'-deoxy-5-ethyl-beta-4'-thiouridine (4'-S-EtdU)Shown to be a more potent inhibitor of gammaherpesvirus infection than acyclovir.2'-Deoxy-5-ethyl-beta-4'-thiouridine inhibits replication of murine gammaherpesvirus and delays the onset of virus latency.10628807
BP008The compound reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC(50)) and selective index value of 4.1 ? 0.7 nM and >12,195, respectively.Resistance analysis and characterization of a thiazole analogue, BP008, as a potent hepatitis C virus NS5A inhibitor. Hepatitis C virus (HCV) is a global health problem, affecting approximately 3% of the world's population.22006008
2,6-difluoro analogue (4r)With potent antiviral activity (IC50 = 0.087 ? 0.002 microM)Low cytotoxicity (CC50 = 90.6 ? 2.06 microM)Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0.087 ? 0.002 microM), low cytotoxicity (CC50 = 90.6 ? 2.06 microM), sensitivity to nucleoside analogue-resistant HBV mutants, and synergistic effect with nucleoside analogues in HepG2.2.15 cells.27989113
4-{[4-({(3R)-1-Butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5dioxo-1,4,9-triazaspiro [5.5]undec-9-yl}methyl)phenyl]oxy}benzoic acid hydrochloride (873140)A potent allosteric noncompetitive HIV entry inhibitorThe CCR5 receptor-based mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor.15644495
Furanyl-containing analog UC10, UC040, UC82, and UC781The most potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication and a promising candidate for further development.From these studies, the furanyl-containing analog UC10 was identified as the most potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication and a promising candidate for further development.9087499
Dihydrotriazolopyrimidine derivative, hybrid molecules 36 and 37Compound 36 that emerged as the most potent PA-PB1 interaction inhibitor (IC50 = 1.1 microM) among all the small molecules reported so far.A Broad Anti-influenza Hybrid Small Molecule That Potently Disrupts the Interaction of Polymerase Acidic Protein-Basic Protein 1 (PA-PB1) Subunits. Very interesting results were obtained with the hybrid molecules 36 and 37, designed by merging some peculiar structural features known to impart PA-PB1 interaction inhibition, with compound 36 that emerged as the most potent PA-PB1 interaction inhibitor (IC50 = 1.1 microM) among all the small molecules reported so far.25856229
Inhibitors (compounds 1 and 2) of malarial aspartyl protease, plasmepsin-IIcompounds 1 and 2 show promising inhibitory activity against HIV-1 protease variants and hence are good candidates for further development to enhance their potency against NL4-3 as well as MDR HIV-1 protease variants.Two potent inhibitors (compounds 1 and 2) of malarial aspartyl protease, plasmepsin-II, were evaluated against wild type (NL4-3) and multidrug-resistant clinical isolate 769 (MDR) variants of human immunodeficiency virus type-1 (HIV-1) aspartyl protease.22469467
5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide analoguesThese compounds satisfy two structural requirements known for potent inhibition of HIV-1 IN catalysis: a metal chelating moiety and a hydrophobic functionality necessary for selectivity against the strand transfer reaction.Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase. Most of the new compounds described herein are potent and selective for the strand transfer reaction and show antiviral activity in cell-based assays.25150089
UV-4 or N-(9-methoxynonyl)-1-deoxynojirimycinUV-4, and its hydrochloride salt known as UV-4B, is highly potent against dengue virus in vitro and promotes complete survival in a lethal dengue virus mouse model.UV-4 treatment did not affect the development of protective antibody responses after either influenza infection or vaccinationIn vivo therapeutic protection against influenza A (H1N1) oseltamivir-sensitive and resistant viruses by the iminosugar UV-4. Our lead iminosugar analog called UV-4 or N-(9-methoxynonyl)-1-deoxynojirimycin inhibits activity of endoplasmic reticulum (ER) ?-glucosidases I and II and is a potent, host-targeted antiviral candidate.25786028
Alkoxyalkyl esters of 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl) adenineAlkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more active than unmodified (S)-HPMPA on the basis of their 50% effective concentrations in 2.2.15 cells.Alkoxyalkyl esters of 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl) adenine are potent and selective inhibitors of hepatitis B virus (HBV) replication in vitro and in HBV transgenic mice in vivo. Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro.19398648
S/GSK1349572Inhibited HIV replication with low-nanomolar or subnanomolar potency and with a selectivity index of 9,400.In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. S/GSK1349572 is a next-generation HIV integrase (IN) inhibitor designed to deliver potent antiviral activity with a low-milligram once-daily dose requiring no pharmacokinetic (PK) booster.21115794
BMS-790052Inhibits hybrid replicons containing HCV genotype-4 NS5A genes with 50% effective concentrations (EC(50)s) ranging from 7 to 13 pM.In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A. The antiviral profile of BMS-790052, a potent hepatitis C virus (HCV) replication complex inhibitor targeting nonstructural protein NS5A, is well characterized for HCV genotype-1.22203595
PSI-352938The effective concentration required to achieve 50% inhibition for PSI-352938, determined using genotype 1a-, 1b-, and 2a-derived replicons stably expressed in the Lunet cell line, were 0.20, 0.13, and 0.14 microM, respectively.Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of ?-D-2'-deoxy-2'-?-fluoro-2'-?-C-methylguanosine. PSI-352938 is a novel cyclic phosphate prodrug of ?-D-2'-deoxy-2'-?-fluoro-2'-?-C-methylguanosine 5'-monophosphate that has potent activity against hepatitis C virus (HCV) in vitro.21444700
Cepharanthine hydrochloride (CH)CH inhibited replication and HBeAg production by either wild-type or lamivudine-resistant HBV clinical isolates in a dose-dependent mannerIn vitro activity of cepharanthine hydrochloride against clinical wild-type and lamivudine-resistant hepatitis B virus isolates. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound, has been reported to possess potent activity against various viruses.22387093
TMC125In high-MOI experiments, 1 muM TMC125 completely inhibited the breakthrough of resistant virus from wild-type and NNRTI-resistant HIV-1, in contrast to efavirenz and nevirapine.TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. TMC125 is a potent new investigational nonnucleoside reverse transcriptase inhibitor (NNRTI) that is active against human immunodeficiency virus type 1 (HIV-1) with resistance to currently licensed NNRTIs.16188980
BI 207127Rapid virological response (RVR; HCV RNA <15 IU/ml) at day 28 occurred in 11/19 TN and 4/30 TE patients treated with BI 207127.BI 207127 in combination with PegIFN/RBV demonstrated strong antiviral activity with a favourable safety and tolerability profile. The best benefit/risk ratio was observed at 600 mg.Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin. BACKGROUND & AIMS: BI 207127 is a potent non-nucleoside hepatitis C virus (HCV) NS5B polymerase inhibitor in vitro.22414766
1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracilsThe candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents. Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1.21903401
PSI-353661, a phosphoramidate prodrug of 2'-deoxy-2'-fluoro-2'-C-methylguanosine-5'-monophosphatePSI-352666 is equally active against wild-type NS5B and NS5B containing the S282T amino acid alteration.Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661.21600932
Spiroadamantane amine (3)Inhibits both the M2-WT and M2-V27A mutant with IC50 values of 18.7 and 0.3 microM, respectivelyAn M2-V27A channel blocker demonstrates potent in vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses. Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus.28087313
N-[4-Chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furanca rbothioamide (UC781)1:1 molar combination of UC781 and 3'-azido-3'-deoxythymidine (AZT) showed high-level synergy in inhibiting the replication of AZT-resistant virus, implying that UC781 can restore antiviral activity to AZT against AZT-resistant HIV-1.The thiocarboxanilide nonnucleoside inhibitor UC781 restores antiviral activity of 3'-azido-3'-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus type 1. N-[4-Chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furanca rbothioamide (UC781) is an exceptionally potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.9925515
Analogues of the dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) [D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid]Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM.Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.9986720
N-acyl azacyclic ureas (II)The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains. As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands.16203141
Benzylpyridinones Compounds 14, 19, and 27IC(50) values ranging from 0.2 to 6 nMSynthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors. Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities.11052800
Monosubstituted 5'-O-fatty acyl derivatives of 3TCThe monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC(50) = 0.2-2.3 microM) were more potent than the corresponding monosubstituted N(4)-fatty acyl (EC(50) = 0.4-29.4 microM) and 5'-O-N(4)-disubstituted (EC(50) = 72.6 to >154.0 microM) derivatives of the nucleoside. 5'-O-Myristoyl (16) and 5'-O-12-azidododecanoyl derivatives (17) were found to be the most potent compounds (EC(50) = 0.2-0.9 microM) exhibiting at least 16-36-fold higher anti-HIV activity against cell-free virus than 1 (EC(50) = 11.4-32.7 microM).Synthesis and biological evaluation of fatty acyl ester derivatives of (-)-2',3'-dideoxy-3'-thiacytidine. A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. 22533850
Beta-d-3'-fluoro-2',3'-unsaturated nucleosidesd-3'-fluoro-2',3'-unsaturated nucleosides against HIV-1 in human peripheral blood mononuclear cells, from which we found that the cytosine derivative 26 was the most potent among the synthesized compounds.Synthesis, structure-activity relationships, and drug resistance of beta-d-3'-fluoro-2',3'-unsaturated nucleosides as anti-HIV Agents. Our recent studies demonstrated that d- and l-2'-fluoro-2',3'-unsaturated nucleosides (d- and l-2'-F-d4Ns) display moderate to potent antiviral activities against HIV-1 and HBV.15189036
T-1249Antiretroviral activity, as measured by levels of HIV-1 RNA, was not predicted by baseline susceptibility to T-1249 or to ENF; genotypic substitutions that emerged during T-1249 treatment were identified in virus from some patientsT-1249 retains potent antiretroviral activity in patients who had experienced virological failure while on an enfuvirtide-containing treatment regimen. BACKGROUND: T-1249 is a 39-amino acid synthetic peptide fusion inhibitor (FI) shown to preserve antiretroviral activity in vitro against human immunodeficiency virus (HIV) isolates that have decreased susceptibility to enfuvirtide (ENF).15747252
Peramivir conjugates 8 and 9Thus, conjugates 8 and 9 offer better effect to protect MDCK cells from infection of H275Y virus with low EC50 value (?17 nM)The C2-OH group of peramivir is elaborated to link with caffeate derivatives, giving the desired conjugates 8 and 9 that possess potent NA inhibitory activity against both wild-type and H275Y viruses with the IC50 values in nanomolar range.29324342
BMS-986001BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nMThe Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.26392486
(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)The phosphoramidate derivatives of BVDU that contain L-alanine exhibited potent anti herpes simplex virus type 1 and varicella-zoster virus activity but lost marked activity against thymidine kinase-deficient virus strains.The phosphoramidate derivatives of BVDU that contain L-alanine exhibited potent anti herpes simplex virus type 1 and varicella-zoster virus activity but lost marked activity against thymidine kinase-deficient virus strains.11900348
PF-00868554EC(50) of 0.059 microMPreclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Our results indicate that PF-00868554 has potent in vitro antiviral activity against a majority (95.8%) of genotype 1a and 1b replicons, with an overall mean EC(50) of 0.059 microM.19307358
Betulinic acid derivative IC9564IC9564 blocked HIV type 1 (HIV-1) envelope-mediated membrane fusion.Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. The betulinic acid derivative IC9564 is a potent anti-human immunodeficiency virus (anti-HIV) compound that can inhibit both HIV primary isolates and laboratory-adapted strains.11120945
Several 3-(2-methylfuranyl)- and 3-(2-methylthienyl)-thiocarboxanilide ester, (thio)ether, and oxime ether derivatives UC-8250% effective concentration, 0.009 to 0.021 microM and 0.015 to 0.021 microM respectivelySeveral 3-(2-methylfuranyl)- and 3-(2-methylthienyl)-thiocarboxanilide ester, (thio)ether, and oxime ether derivatives showed exquisitely potent antiviral activity against wild-type HIV-1 (50% effective concentration, 0.009 to 0.021 microM).8726019
Spirodiketopiperazine (SDP) derivative, AK602/ONO4128/GW87314050% inhibitory concentration values of 0.1 to 0.6 nMSpirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. 15280474
2-chloro-8-phenylthiomethyl analogue 37Displayed sub-100 nM activity against all HIV-1 RT enzymes tested.Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 8. 8-Aryloxymethyl- and 8-arylthiomethyldipyridodiazepinones. The most potent compound was 2-chloro-8-phenylthiomethyl analogue 37 which displayed sub-100 nM activity against all HIV-1 RT enzymes tested.9685236
1,2,3-Triazole; 4-OxoquinolineOxoquinoline derivative 1i with an EC50 of 0.2 microMOxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity.26643220
BMS-23263250% effective concentration [EC(50)], 2.6 to 5.3 nM; EC(90), 9 to 15 nMIn vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632.10952574
5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamideVery potent and selective anti-HIV-1 activity against some mutants carrying NNRTI resistant mutations at positions 103 and 181 of the reverse transcriptase.Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants.16305512
NITD008In cell culture, the compound inhibits EV71 at a 50% effective concentration of 0.67 microM and a 50% cytotoxic concentration of 119.97 microM.Inhibition of enterovirus 71 by adenosine analog NITD008. Here we report that NITD008 has potent antiviral activity against EV71.25100827
Tetra-O-glycyl-NDGA (G(4)N)In yield reduction assays, G(4)N inhibited replication of laboratory and clinical strains of wild type HSV-1 and ACV-resistant (HSV-1(R)) strains of HSV-1 in a dose-dependent manner, with average IC(50) values of 4.7 and 3.2 microM against wild-type and HSV-1(R) strains, respectively.Inhibition of HSV-1 replication and reactivation by the mutation-insensitive transcription inhibitor tetra-O-glycyl-nordihydroguaiaretic acid. Methylated derivatives of nordihydroguaiaretic acid (NDGA)were previously shown to be potent mutation-resistant inhibitors of herpes simplex virus type 1 (HSV-1) which target Sp1 protein binding to critical viral promoters.12719005
Maraviroc (UK-427,857)Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes.Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties.16251317
(-)-Beta-D-1',3'-Dioxolane guanosine (DXG) and 2,6-diaminopurine (DAPD) dioxolanyl nucleosideIn cellular toxicity analyses, DXG and DAPD had 50% cytotoxic concentrations of greater than 500 microM when tested in peripheral blood mononuclear cells and a variety of human tumor and normal cell linesMechanism of action and in vitro activity of 1',3'-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants. (-)-Beta-D-1',3'-Dioxolane guanosine (DXG) and 2,6-diaminopurine (DAPD) dioxolanyl nucleoside analogues have been reported to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1).10508010
(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4yl)thymine (DOT)Has potent in vitro activity against wild-type and nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV.Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent. (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4yl)thymine (DOT) is a thymidine analogue that has potent in vitro activity against wild-type and nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV.17542153
MIV-150 with zinc acetate (ZA)While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 microM.MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1. We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG.28812250
GS-5806[EC50] = 0.43 nMIn summary, GS-5806 is a potent and selective RSV fusion inhibitor with antiviral activity against a diverse set of RSV clinical isolates.26666922
ca603ca603 inhibits rhinovirus replication by interaction with the VP1 protein and, by this, allows to further expand the chemical diversity of capsid-binding molecules.In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses. BACKGROUND: Rhinovirus infections do not only cause common colds, but may also trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). It is confirmed that ca603 inhibits rhinovirus replication by interaction with the VP1 protein and, by this, allows to further expand the chemical diversity of capsid-binding molecules.26169596
D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosidesAmong the synthesized L-series nucleosides, compounds 18, 19, 26 and 28 exhibited moderate antiviral activity (EC50 7.1 microM, 6.4 microM, 10.3 microM, and 20.7 microM, respectively), while among the D-series, the guanosine analogue (35, D-3'-F-C-d4G) exhibited the most potent anti-HIV activity (EC50 0.4 microM, EC90 2.8 microM)Among the synthesized L-series nucleosides, compounds 18, 19, 26 and 28 exhibited moderate antiviral activity (EC50 7.1 microM, 6.4 microM, 10.3 microM, and 20.7 microM, respectively), while among the D-series, the guanosine analogue (35, D-3'-F-C-d4G) exhibited the most potent anti-HIV activity (EC50 0.4 microM, EC90 2.8 microM).17373782
3'-fluoro-3'-deoxythymidine (FLT)IC(50) values for FLT of 0.0014-0.0168 microMAnti-HIV type 1 activity of 3'-fluoro-3'-deoxythymidine for several different multidrug-resistant mutants. The objective of this work was to test the antiviral activity of a potent nucleoside reverse transcriptase inhibitor, 3'-fluoro-3'-deoxythymidine (FLT), on both a wild-type human immunodeficiency virus (HIV-1) isolate and multidrug-resistant HIV-1 patient isolates.11282008
Bicyclam derivative JM3100JM3100 exhibits anti-HIV potency at concentrations ranging from 0.001 to 0.01 micrograms/mlAntiviral activity of the bicyclam derivative JM3100 against drug-resistant strains of human immunodeficiency virus type 1. Bicyclams have recently been identified as potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) replication.8739608
BMS-955176BMS-955176 exhibits potent activity (50% effective concentration [EC50], 3.9 +/- 3.4 nM ) toward a library (n = 87) of gag/pr recombinant viruses representing 96.5% of subtype B polymorphic Gag diversity near the CA/SP1 cleavage site.BMS-955176 exhibits potent activity (50% effective concentration [EC50], 3.9 ? 3.4 nM [mean ? standard deviation]) toward a library (n = 87) of gag/pr recombinant viruses representing 96.5% of subtype B polymorphic Gag diversity near the CA/SP1 cleavage site.27090171
CGP 53437The replication of HIV-1/LAV, HIV-1/Z-84, and HIV-1/pLAI was inhibited with a 90% effective dose of 0.1 microM in acutely infected MT-2 cells.The 50% cytotoxic dose was 100 microM.CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type 1 protease with potent antiviral activity. CGP 53437 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease containing a hydroxyethylene isostere.8257128
hexadecyloxypropyl-(S)-HPMPA [HDP-(S)-HPMPA] and octadecyloxyethyl-(S)-HPMPA [ODE-(S)-HPMPA]Ec50 is 0.4 to 0.7 nanomolar, active against HIV variantsAlkoxyalkyl esters of (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine are potent inhibitors of the replication of wild-type and drug-resistant human immunodeficiency virus type 1 in vitro.16870786
A titanium containing polyoxotungstate, PM-523 and vanadium substituted polyoxotungstate, PM-1001PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV). PM-1001 has antiviral activity against FluV A, RSV, parainfluenza virus (PfluV) type 2, Dengue fiver virus, HIV-1 and SARS coronavirus in vitro.A titanium containing polyoxotungstate, PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV) activities in vitro.16737794
Compound-13 (P1-substituted HIV PIs)Compound 13 demonstrated the best balance of potency against drug resistant strains of HIVA series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized.21899332
Compound 2, a copper(I)-catalyzed 1,2,3-triazole derivativeIC 50 = 6.0 nM and 15.7 nM against wild -type protease and ultidrug-resistant 6X protease mutant respectively.A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant. Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance.18823110
2'-deoxy-4'-C-ethynyl-2-fluoroadenosinePotent to all human immunodeficiency viruses type 1 (HIV-1s) including multidrug-resistant HIV-1 and has a low toxicity2'-deoxy-4'-C-ethynyl-2-fluoroadenosine, a nucleoside reverse transcriptase inhibitor, is highly potent against all human immunodeficiency viruses type 1 and has low toxicity. An idea to use 4'-C-substituted-2'-deoxynucleoside derivatives was proposed based on a working hypothesis to solve the problems of existing acquired immune deficiency syndrome chemotherapy (highly active antiretroviral therapy).16795005
NcRTIs (compound A)Treatment of infections with K65R substitution-containing HIV-1 virusesSubtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor. Compound A is a novel nucleotide-competing HIV-1 reverse transcriptase (RT) inhibitor (NcRTI) that selects for a unique W153L substitution that confers hypersusceptibility to tenofovir, while the K65R substitution in RT confers resistance against tenofovir and enhances susceptibility to NcRTIs.25779585
Apricitabine (ATC)Promising antiviral activity and effective treatment-experienced patients with M184VAntiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. Apricitabine (ATC) is a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor (NRTI) with significant antiviral activity in vitro, including activity against HIV-1 with reverse transcriptase mutations that confer resistance to other NRTIs.21054750
Calanolide A, costatolide, and dihydrocostatolideAnti-HIVThe calanolide isomers represent a novel and distinct subgroup of the NNRTI family, and these data suggest that a compound of the calanolide A series, such as costatolide, should be evaluated further for therapeutic use in combination with other anti-HIV agents.10428899
WPR-6 : 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dioneEC50 of 2 to 4nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391.The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes26055365
Pleconaril variants with F, Cl, Br, CH3, OH and aromatic ring substitutionsPleconaril variants with F, Cl, Br, CH3, OH and aromatic ring substitutions were shown to be effective alternatives to Oseltamivir as anti influenza drugs.In-Silico screening of Pleconaril and its novel substituted derivatives with Neuraminidase of H1N1 Influenza strain. Neuraminidase (NA) is a prominent surface antigen of Influenza viruses, which helps in release of viruses from the host cells after replication.22340192
PF-00868554, non-nucleoside inhibitor (NNI)Activity against hepatitis C virusThe obtained computational results will have important value for the rational design of novel non-nucleoside inhibitors targeting HCV NS5B polymerase.24452008
TBZE-029 {1-(2,6-difluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole}Inhibits enterovirus replicationThe thiazolobenzimidazole TBZE-029 inhibits enterovirus replication by targeting a short region immediately downstream from motif C in the nonstructural protein 2C.18337578
Morus alba germin-like proteinSilkworm fecal matter is considered one of the richest sources of antimicrobial and antiviral protein (substances)Molecular cloning and characterization of novel Morus alba germin-like protein gene which encodes for a silkworm gut digestion-resistant antimicrobial protein. Silkworm fecal matter is considered one of the richest sources of antimicrobial and antiviral protein (substances) and such economically feasible and eco-friendly proteins acting as secondary metabolites from the insect system can be explored for their practical utility in conferring broad spectrum disease resistance against pathogenic microbial specimens.23284650
BP13944BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC50) of 1.03 +/- 0.09 microM.A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease. Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year.24145533
Arylthio isopropyl pyridinylmethylpyrrolemethanols (AThPs)Docking experiments of the potent inhibitors 4k (IC(50) = 0.24 microM, SI = 167) and 5e (IC(50) = 0.11 microM, SI > 1667) of wild-type RT prompted the synthesis and biological evaluation of novel AThP derivatives featuring a number of polar groups in position 3 of the pyrrole ring and larger and more hydrophobic alicyclic substituents in place of the isopropyl group at position 4.Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies17089434
KINK-20, a synthetic phosphocholine lipid-AZT conjugateEC50 values were 0.01 and 0.03 microM for INK-20 and 0.0005 and 0.33 microM for AZT, respectively.Synthesis and evaluation of a novel synthetic phosphocholine lipid-AZT conjugate that double-targets wild-type and drug resistant variants of HIV.15043162
N(4)-octyl-6,6-dimethyl-N(2)-(4-methylbenzyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine (HM-242)Potent virucidal activity against enveloped viruses such as influenza virus and herpes simplex virus.The antimicrobial activities of N(4)-octyl-6,6-dimethyl-N(2)-(4-methylbenzyl)-1,6-dihydro-1,3,5-triazine-2,4-diam ine (HM-242), a novel synthetic compound, were compared with those of chlorhexidine gluconate (CHG).19575042
Alcian Blue (AB)Novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV.These data suggest that AB is likely endowed with carbohydrate-binding properties and can be considered an important lead compound in the development of novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV.19721061
Indolocarbazole compounds, G?6976 and NGIC-IIndolocarbazole compounds are potent pUL97 inhibitors and, therefore, represent novel candidates for antiviral drugs that target viral protein kinase functionsBased on the phosphorylation of ganciclovir (GCV), a novel quantification system for pUL97 kinase activity was established: the phosphorylated form of GCV exerts an easily quantifiable cytotoxic effect in transfected cells.11369889
Sho-seiryu-to (SST)SST is a novel compund with potential as an anti-HCMV.These results suggest that SST is a novel compund with potential as an anti-HCMV.16542001
lersivirine (UK-453,061)Binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC(50)s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets.The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC(50)s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets.20660667
Raoulic acidraoulic acid was found to possess broad-spectrum antiviral activity against six HRVs with a 50% inhibition concentration of less than 9.5 microg/mLCollectively, the results demonstrate that raoulic acid is a novel therapeutic candidate for two different groups of human rhinovirus.20412019
Isothiafludine (NZ-4)NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC?? value of 1.33 micromol/L, whereas the compound inhibited the cell viability with an IC?? value of 50.4 micromol/L.Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation. To investigate the action of isothiafludine (NZ-4), a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in vitro and in vivo.24487969
Benzenesulfonyl matrinane, 35dPromising anti-enteroviral candidate for the treatment of various diseases infected with coxsackieviruses.The optimized 35d showed the broad-spectrum anti-coxsackieviruse effects, an excellent pharmacokinetics and a good safety profile.SAR evolution and discovery of benzenesulfonyl matrinanes as a novel class of potential coxsakievirus inhibitors.Fifty-one novel 12N-substituted matrinic acid derivatives were synthesized and evaluated for their anti-coxsackievirus B3 activities.26867658
THC19THC19 acts at a relatively early stage of the viral lifecycle.This compound had no cytotoxic effects and did not disrupt cell cycle progression or induce apoptosis in MDCK cells as confirmed by WST-1 assays, flow cytometry analysis, and caspase-3 assays.Taken together, these results suggest that influenza virus PA protein is a potential target for, and may aid the development of, novel compounds that inhibit influenza A virus replication.22441116
R1479Potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro.No resistance to R1479 was observed after 14 days of treatment with R1626.Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C. The nucleoside analog R1479 is a potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro.18553458
Cyanovirin-N (CV-N)CV-N and related homologs showed highly potent antiviral activity against almost all strains of influenza A and B virus, including clinical isolates and a neuraminidase inhibitor-resistant strain (EC(50) = 0.004 to 0.04 micro g/ml).Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. . The novel antiviral protein cyanovirin-N (CV-N) was initially discovered based on its potent activity against the human immunodeficiency virus (HIV).12878514
TTP-8307A potent inhibitor of the replication of several rhino- and enteroviruses.Mutations in the nonstructural protein 3A confer resistance to the novel enterovirus replication inhibitor T A novel compound, TTP-8307, was identified as a potent inhibitor of the replication of several rhino- and enteroviruses.19237651
VRX-480773Inhibits viruses from efavirenz-resistant molecular clones and most NNRTI-resistant clinical HIV-1 isolates testedIn this study, we report a novel and potent NNRTI, VRX-480773, that inhibits viruses from efavirenz-resistant molecular clones and most NNRTI-resistant clinical HIV-1 isolates tested.17116677
ObatoclaxActive against alphaviruses, like chikungunya virus (50% effective concentration [EC50] = 0.03 microM) and Semliki Forest virus (SFV; EC50 = 0.11 microM).In conclusion, obatoclax is a novel inhibitor of endosomal acidification that prevents viral fusion and that could be pursued as a potential broad-spectrum antiviral candidate.27993855
Benzodiazepine derivative (compound 7)Compound 7 was validated as an inhibitor of infectious EBOV and Marburg virus (MARV) in cell-based assays, with 50% inhibitory concentrations (IC(50)s) of 10 microM and 12 microM, respectively.In summary, we have identified a novel series of benzodiazepine compounds that are suitable for optimization as potential inhibitors of filoviral infection.21270170
2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772)Serum concentrations of DB772 sufficient to inhibit viral replication in calves PI with BVDV types 1 and 2No adverse effects of DB772 administration were detectedThe purpose of this research was to initiate evaluation of the pharmacokinetic and safety data of a novel antiviral agent in BVDV-free calves and to assess the antiviral efficacy of the same agent in PI calves.22182713
4-guanidino-Neu5Ac2en, neuraminidase (NA)-specific inhibitorThe lowest resistance in cell culture was seen to zanamivirThe search for compounds with altered pharmacological properties has led to the identification of a novel series of influenza virus NA inhibitors in which the triol group of zanamivir has been replaced by a hydrophobic group linked by a carboxamide at the 6 position (6-carboxamide).9499107
SC93305Highly effective not only against different HSV-1 and HSV-2 strains but also towards ACV- and multi-resistant HSV-1 and HSV-2 isolatesIn the current study we present SC93305 as a novel potent antiviral substance that proved to be highly effective not only against different HSV-1 and HSV-2 strains but also towards ACV- and multi-resistant HSV-1 and HSV-2 isolates.29155164
GS-9160GS-9160 has potent and selective antiviral activity in primary human T lymphocytes producing a 50% effective concentration (EC(50)) of approximately 2 nM, with a selectivity index (50% cytotoxic concentration/EC(50)) of approximately 2,000. The antiviral potency of GS-9160 decreased by 6- to 10-fold in the presence of human serum.Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. GS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN) that specifically targets the process of strand transfer. It is an authentic inhibitor of HIV-1 integration, since treatment of infected cells results in an elevation of two-long terminal repeat circles and a decrease of integration junctions.19104010
GS-9451GS-9451 200 mg/day or 400 mg/day demonstrated potent antiviral activity in both HCV genotype 1a- and 1b-infected patients.No resistance mutations were detected with GS-9451 60 mg/day.A Phase I, randomized, placebo-controlled, 3-day, ascending-dose study of GS-9451, an NS3/4A protease inhibitor, in genotype 1 hepatitis C patients. GS-9451 is a novel inhibitor of the HCV NS3/4A protease and demonstrates potent in vitro suppression of HCV genotype 1 replicons.23047118
A-315675Influenza virus neuraminidase (NA) inhibitor that has potent enzyme activity and is highly active in cell culture against a variety of strains of influenza A and B viruses.A-315675 is a novel influenza virus NA inhibitor that has potent enzyme activity and is highly active in cell culture against a variety of strains of influenza A and B viruses.11991966
(1S,2S,3R,4R)-3-[(1S)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-h ydroxy-cyclopentanecarboxylic acid (RWJ-270201, BCX-1812)The 50% effective concentration (EC(50)) values for RWJ-270201 against wild-type and resistant viruses, determined by using a cytopathic effect inhibition assay, were 0.007 and 23 microM, respectively.Characterization of an influenza A (H3N2) virus resistant to the cyclopentane neuraminidase inhibitor RWJ-270201.11675142
RD4-2217, thiadiazole (TDA) derivativesIt inhibited replication of the HTLV-IIIB strain in MT-4 cells at a concentration of 6 nM.In an attempt to develop more effective and pharmacologically favorable compounds, novel TDA derivatives have been synthesized and examined for their anti-HIV-1 activity in vitro.9159403
KU-55933Inhibitor of ATM kinase activity, capable of suppressing the replication of both wild-type and drug-resistant HIV-1Here we show that the activity of HIV-1 integrase stimulates an ataxia-telangiectasia-mutated (ATM)-dependent DNA damage response, and that a deficiency of this ATM kinase sensitizes cells to retrovirus-induced cell death. Consistent with these observations, we demonstrate that a novel and specific small molecule inhibitor of ATM kinase activity, KU-55933, is capable of suppressing the replication of both wild-type and drug-resistant HIV-1.15834407
Cyclic urea amide, SD146IC90 is 5.1 nMCyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV. Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR.9003516
EDP-239A single 100-mg dose of EDP-239 resulted in reductions in HCV genotype 1a viral RNA of >3 log10 IU/ml within the first 48 h after dosing and reductions in genotype 1b viral RNA of >4-log10 IU/ml within 96 hPreclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A Inhibitor, EDP-239. EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated in vitro and in vivo EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6.27503640
Benzimidazole Derivative (B5)Inhibits the HCV life cycle by blocking virus entryIn conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.IMPORTANCE: In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice.27412600
Cyclosporin A (CsA) analog, CPI-431-32As a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections.Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI), including a novel cyclosporin A (CsA) analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection.26263487
SCH 900518 (narlaprevir)EC(90)) of 40 nMPreclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease. Small-molecule hepatitis C virus (HCV) NS3 protease inhibitors such as boceprevir (SCH 503034) have been shown to have antiviral activity when they are used as monotherapy and in combination with pegylated alpha interferon and ribavirin in clinical trials.20308381
N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivativesEC50 is 0.228 microMViral infectivity factor (Vif) is protective against APOBEC3G (A3G)-mediated viral cDNA hypermutations, and development of molecules that inhibit Vif mediated A3G degradation is a novel strategy for blocking HIV-1 replication.28235704
Piperidinylamino-diarylpyrimidine (pDAPY) derivativesEC50 = 0.047 and 4.6 microM against both wild-type and drug-resistant mutant virus strains (K103N+Y181C RT) of HIV-1Exploring these hybrid molecules with dual binding conformations might provide optional chemical scaffolds as novel HIV-1 reverse transcriptase inhibitors (HIV-1 NNRTIs).24239481
Pleconaril, guanidine-HCl, and oxoglaucine (PGO)Decreased infectious virus contentThe most important achievement of our previous studies was the development of a novel scheme for in vivo application of a triple combination of EV inhibitors with different modes of action against Coxsackievirus B (CVB) infections in mice.26196747
Pyrrolobenzoxazepinones (PBOs) derivativesPotent against the most common mutant enzymes, including the highly resistant K103N mutant strain.Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents.16279773
8-hydroxyquinoline tetracyclic lactamAntiviral activity against HIV-1A novel series of HIV-1 integrase strand transfer inhibitors were designed using the venerable two-metal binding pharmacophore model and incorporating structural elements from two different literature scaffolds.27092410
Calix[4]arene-based ?-diketo derivativesInhibit strand transfer (ST) with IC50 values between 5.9 and 21.2 microMDocking studies revealed the predominant binding modes that were distinct from the binding modes of raltegravir, which suggests a novel binding region in the IN active site.25682937
TMC114EC50s of <10 nMTMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. The purpose of this study was to characterize the antiviral activity, cytotoxicity, and mechanism of action of TMC114, a novel human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI).15917527
LeflunomideInhibits the production of multiple clinical CMV isolates (including multi-drug-resistant virus) in both human fibroblasts and endothelial cells.These findings imply that leflunomide, an effective immunosuppressive agent, shows potential to concurrently attenuate a major complication of immunosuppression, CMV disease, by a novel mechanism of antiviral activity.10702725
AIC246 (Letermovir)AIC246 blocks viral replication without inhibiting the synthesis of progeny HCMV DNA or viral proteinsThe novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.21752907
ACH-806This compound was synergistic with NS3 protease inhibitors and NS5B nucleoside and nonnucleoside polymerase inhibitors.ACH-806 is a hepatitis C virus NS4A inhibitor with a novel mechanism of action and resistance pathway.18332167
Alpha-hydroxy-glycineamide (alpha-HGA)Inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitorsAs an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action.18644965
GRL-0739, a novel nonpeptidic HIV-1 protease inhibitor containing tricycle (cyclohexyl-bis-tetrahydrofuranylurethane [THF]) and a sulfonamide isostereHighly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0019 to 0.0036 microM)M, with minimal cytotoxicity (50% cytotoxic concentration [CC50], 21.0 microM)A novel tricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor, GRL-0739, effectively inhibits the replication of multidrug-resistant HIV-1 variants and has a desirable central nervous system penetration property in vitro25691652
Pradimicin A (PRM-A)It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations.PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.17050611
GS-9451In multiple GT1a and GT1b replicon cell lines, GS-9451 had mean 50% effective concentrations (EC50s) of 13 and 5.4 nM, respectively, with minimal cytotoxicityPreclinical characterization of the novel hepatitis C virus NS3 protease inhibitor GS-9451. GS-9451 is a selective hepatitis C virus (HCV) NS3 protease inhibitor in development for the treatment of genotype 1 (GT1) HCV infection.23939899
MK-4519(EC(50)) of 1.8 nM and MK-4519 is highly active against genotype 1b HCVPharmacodynamic analysis of a serine protease inhibitor, MK-4519, against hepatitis C virus using a novel in vitro pharmacodynamic systemThe development of new antiviral compounds active against hepatitis C virus (HCV) has surged in recent years.22155837
2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T)The purified RT of mutants with the P119S/M184V and T165A/M184V mutations were inhibited by 4'-Ed4TTP with 8- to 13-fold less efficiency than wild-type RT.Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile.2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T), a derivative of stavudine (d4T), has potent activity against human immunodeficiency virus and is much less inhibitory to mitochondrial DNA synthesis and cell growth than its progenitor, d4T.19704131
Samatasvir (IDX719)EC50s falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicon. The EC90/EC50 ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 microM provided a selectivity index of >5 ? 10(7)In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus. The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection.24867983
H1PVATInhibitor of poliovirus replication that targets VP1A novel small molecule, H1PVAT, was identified as a potent and selective inhibitor of the in vitro replication of all three poliovirus serotypes, whereas no activity was observed against other enteroviruses.25043639
AzvudineHighly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nanoM), HIV-2 (EC(50)s ranging from 0.018 to 0.025 nanoM) and NRTI-resistant strains (L74V and T69N).Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus.25144636
BPR2-D2BPR2-D2 exhibited an excellent antiviral efficacy for the oseltamivir-resistant virus (EC(50) ranging from 0.021 to 0.040 microMBPR2-D2 was identified as a novel inhibitor against influenza virus from a hit obtained from high throughput screening of 20 000 or more compounds.19892833
SC29EKSC29EK blocked the replication of T-20-resistant HIV-1 strains and maintained antiviral activity even in the presence of high serum concentrations (up to 50%).We have developed a novel HIV fusion inhibitor, SC34EK, which is a gp41-derived 34-amino-acid peptide with glutamate (E) and lysine (K) substitutions on its solvent-accessible site that stabilize its alpha-helicity.19114674
DMP 450 (bis-methanesulfonic acid salt)A plasmid-based, in vivo assay model suggests that maintenance of plasma levels of DMP 450 near the antiviral IC90 suppresses HIV protease activity in the animal.RESULTS: We have synthesized DMP 450 (bis-methanesulfonic acid salt), a water-soluble cyclic urea compound and a potent inhibitor of HIV replication in cell culture that also inhibits variants of HIV with single amino acid substitutions in the protease.8807858
Cyclo-D4GPossessed anti-HIV activityNovel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'-dideoxyguanosine into a viable antiviral agent. Transient kinetic studies with human immunodeficiency virus (HIV) type 1 reverse transcriptase suggest that nucleotide analogs containing the 2',3'-didehydro-2',3'-dideoxy ribose ring structure present in D4T (stavudine) triphosphate are among the most effective alternative substrates.11850281
GRL-057-14, GRL-058-14, and GRL-059-14, all of which contain a P2-amino-substituted-bis-tetrahydrofuranylurethane (bis-THF) and a P2'-cyclopropyl-amino-benzothiazole (Cp-Abt).These PIs not only potently inhibit the replication of wild-type HIV-1 (50% effective concentration [EC50], 0.22 nM to 10.4 nM) but also inhibit multi-PI-resistant HIV-1 variants, including highly DRV-resistant HIVDRV R P51 (EC50, 1.6 nM to 30.7 nM).Combination antiretroviral therapy has achieved dramatic reductions in the mortality and morbidity in people with HIV-1 infection.31085520
tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine)TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively.New antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy.30391482
dihydrofuro[3,4- d]pyrimidine derivatives 13c2 and 13c4Against a wide range of HIV-1 strains carrying single NNRTI-resistant mutations (EC50 = 0.9-8.4 nM), which were remarkably superior to that of etravirine (ETV)the small molecule inhibited HBsAg production and hepatitis B virion secretion (10 ?M) at low micromolar concentrations and was also efficacious against a HBV quadruple mutant (CYEI mutant) resistant to tenofovir.30624934
2,4,5-Trisubstituted PyrimidinesEC50 = 24.4 nMFurthermore, 16c demonstrated favorable pharmacokinetic and safety properties, suggesting the potential of 16c as a promising anti-HIV-1 drug candidate.33734714
ZINC20451377KD of 65.3 nMProlonged therapy with nucleoside/nucleotide analogues targeting the HBV-polymerase may lead to resistance and rarely results in the loss of HBsAg.34083665
Fluorinated cytidine analog, NCC (N-cyclopropyl-4'-azido-2'-deoxy-2'-fluoro-?-d-cytidine)Activity against wild-type hepatitis B virus (HBV) and clinical lamivudine-resistant HBV?Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants.30586543
Ruzasvir (formerly MK-8408)Ruzasvir inhibited HCV RNA replication with 50% effective concentrations (EC50s) of 1 to 4 pM in Huh7 or Huh7.5 cells bearing replicons for HCV genotype 1 (GT1) to GT7. The antiviral activity was modestly (10-fold) reduced in the presence of 40% normal human serumThe interaction of ruzasvir with an NS3/4A protease inhibitor (grazoprevir) and an NS5B polymerase prodrug (uprifosbuvir) was additive to synergistic, with no evidence of antagonism or cytotoxicity.? Inhibition of NS5A has emerged as an attractive strategy to intervene in hepatitis C virus (HCV) replication.30150466
Combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine)Activity against Respiratory Syncytial VirusTherapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses.33946996
Combination therapy of Baloxavir Acid with approved drugsCombinations of BXA and neuraminidase inhibitors (NAIs) or favipiravir had synergistic effects on cell viability against the two influenza A subtypesTherapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses.33049959
Stilbene disulfonic acidsStilbene disulfonic acid derivatives exhibit low to sub-micromolar antiviral activity, and they inhibit integrase through DNA-binding inhibitionChemical structure comparisons enabled the identification of stilbene disulfonic acids as a potential new chemotype.31614773
MonoPEGylated (Gly4Ser)3 derivative of cyanovirin-N : [linker-CV-N (LCV-N)]Potent inhibitory activity against ACV-resistant HSV strains with IC50 values in the nM rangeIn conclusion, we suggest that LCV-N and PEG10k-LCV-N are promising and safe microbicides for the control and/or treatment of ACV-resistant HSV infection.30903291
Cholesterol-modified fusion peptides : LP-83 and LP-86Inhibition of divergent human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV)HIV infection requires lifelong treatment with multiple antiretroviral drugs in a combination, which ultimately causes cumulative toxicities and drug resistance, thus necessitating the development of novel antiviral agents.30867304
Novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamidesActivity against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV)5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring.30411688
Oseltamivir derivatives containing pyridyl groupAmong the tested compounds, compound 23b exhibited potent inhibitory activity against neuraminidase from H5N1 subtype was comparable to oseltamivir carboxylateCytopathic effect inhibition assay in MDCK cells indicated that compound 23b exerted powerful inhibitions on influenza viruses. And compound 23b were nontoxic to MDCK cells. Meanwhile, compound 23b showed high stability towards rat liver microsomes, human liver microsomes and human plasmaDesign, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A.31708183
5-substituted diarylpyrimidine derivativesAll the compounds demonstrated strong inhibition activity against wide-type HIV-1 strain (IIIB) with EC50 values in the range of 2.5 nM ~ 0.93 ?M. Among them, compounds IVB-5-4 and IVB-5-8 were the most potent ones which showed anti-HIV-1IIIB activity much superior than that of Nevirapine, comparable to Efavirenz and EtravirineDesign, synthesis and anti-HIV evaluation of novel 5-substituted diarylpyrimidine derivatives as potent HIV-1 NNRTIs.33979774
ML336, and its analogs, BDGR-4, BDGR-69 and BDGR-70The optimal dosing for maximal protection was observed at 12.5 mg/kg/day, twice daily for 8 daysEfficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses30970271
Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde)EC50 of 16 and 21 ?MCompound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress.33705354
voxilaprevirVosevi? (sofosbuvir, velpatasvir, and voxilaprevir) is now an approved pan-genotypic treatment option for the most difficult-to-cure individuals who have previously failed direct acting antiviral therapy.Furthermore, hepatotoxicity was not observed in Phase 3 clinical trials with voxilaprevir, consistent with our design strategy.Voxilaprevir, in combination with sofosbuvir and velpatasvir, has demonstrated pan-genotypic antiviral clinical activity.31133531