hcv polymerase

Setrobuvir (ANA-598) is an orally active non-nucleoside HCV NS5B polymerase inhibitor with inhibitory effects on de novo RNA synthesis and primer extension with IC50s between 4 and 5 nM. setrobuvir shows good binding affinity for SARS-CoV-2 RdRp and induces inhibition of RdRp.

Sofosbuvir (GS 7977) is a uridine monophosphate analog inhibitor of hepatitis C virus (HCV) polymerase NS5B that is used as an antiviral agent in the treatment of chronic hepatitis C.

VCH-916 is a novel nonnucleoside HCV NS5B polymerase inhibitor.

2’-beta-C-Methyl inosine (2’-C-Methylinosine) is an HCV RNA polymerase inhibitor with antiviral activity and is being studied for the treatment of hepatitis C virus infection.

BILB-1941 (BILB-1941ZW) is an inhibitor of HCV NS5B polymerase and can be used in studies about HCV infection.

TMC647055 Choline Hydroxide Salt is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase which potentially for the treatment of HCV infection. It has nanomolar cellular potency (EC(50) of 82 nM) with minimal associated cell toxicity (CC(

TMC-649128 PM is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) value of 1.2 muM and showing moderate in vivo bioavailability in rat (F=14%).

Filibuvir (PF-00868554) is a selective and noncovalent inhibitor of HCV NS5B RNA-dependent RNA polymerase. Filibuvir inhibits genotype 1a and 1b replicons with EC50s of 59 nM.

IDX184 is a potent, orally active, targeted HCV polymerase inhibitor and nucleoside polymerase.IDX184 effectively inhibits HCV polymerase (IC50=0.31 μM, Ki=52.3 nM). IDX184 is a liver-targeted nucleotide prodrug with anti-HCV activity that inhibits HCV NS5B polymerase and can be used in combination with pegylated interferon-α2a and ribavirin for the primary treatment of chronic hepatitis C. It has been shown to inhibit HCV polymerase and nucleoside polymerase.

Dasabuvir (ABT-333) is a non-nucleoside inhibitor of the hepatitis C virus (HCV) non-structural protein 5B (NS5B), an RNA-dependent RNA polymerase. Upon administration and intracellular uptake, dasabuvir binds HCV NS5B polymerase, blocking viral RNA synthesis and replication. The HCV NS5B protein is essential for the replication of the HCV RNA genome.

Simeprevir (TMC435) is a potent HCV NS3 4A protease inhibitor, and inhibits HCV replication with EC50 of 8 nM.

PSI-6130 (R 1656) is a potent and selective HCV NS5B polymerase inhibitor. PSI-6130 inhibits HCV replication with a mean IC50 of 0.6 μM.

Mericitabine (R-7128) is a nucleoside HCV NS5B polymerase inhibitor. It acts as an RNA chain terminator and prevents the elongation of RNA transcripts during replication.

NM107 (2'-C-Methylcytidine) is a ribonucleoside with broad-spectrum antiviral activity and acts as a nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, demonstrating an EC50 of 1.85 μM in wild-type replicon cells.

PSI-6206 (RO 2433) (RO2433) is a selective HCV RNA polymerase inhibitor.

Nesbuvir is a selective hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent polymerase inhibitor.Nesbuvir has an IC50 of 9 nM against hepatocellular carcinoma cells containing 1b HCV replicons.

NHC-triphosphate tetrasodium, the active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) in its triphosphate form, functions as a weak alternative substrate for viral polymerase, allowing its incorporation into HCV replicon RNA.

NHC-triphosphate triammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a triphosphate form[1]. NHC-triphosphate triammonium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA[1][2]. In an intracellular metabolism assay, HCV replicon cells are treated with 10 μM 3H-labeled NHC, and intracellular nucleotide levels are determined after 1, 2 and 8 hours incubations. NHC is rapidly convered into the mono-, di-, and triphosphate forms, and NHC-TP reaches up to 71.12 pM after 8 hours[1].NHC-triphosphate triammonium (NHC-TP) (5-40 μM) absence leads to full-length polymerization products, it can be a weak alternative substrate. In addition, incorporation of NHC-TP instead of CTP increases the molecular weight of the polymerization product by 16 (one extra oxygen) for each event and an obvious electrophoretic shift is observed in cell-free HCV NS5B polymerization reactions[1].Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC. Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS/MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate (DP) can be observed, while NHC-triphosphate triammonium remains the most abundant metabolite[2].NHC-triphosphate triammonium (NHC-TP) metabolite may directly target the viral polymerase and behave as a nonobligate chain terminator. It plays a prominent role in inhibiting early negative-strand RNA synthesis, either through chain termination or mutagenesis, which may in turn interfere with correct replicase complex formation. [1]. Stuyver LJ,et al. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.Antimicrob Agents Chemother. 2003 Jan;47(1):244-54. [2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.

Ledipasvir (acetone) (GS-5885 acetone) is an HCV NS5A polymerase inhibitor, used for the treatment of hepatitis C virus infection.

BMT-052 is a potent and selective Pan-genotypic HCV NS5B Polymerase Inhibitor (EC50 = 7 nM).

Sofosbuvir-13C-d3 is the 13C and deuterated compound of Sofosbuvir. Sofosbuvir has a CAS number of 1190307-88-0. Sofosbuvir is a uridine monophosphate analog inhibitor of hepatitis C virus (HCV) polymerase NS5B that is used as an antiviral agent in the treatment of chronic hepatitis C.

MK-3281 is a potent, orally bioavailable hepatitis C virus NS5B polymerase finger-loop inhibitor. It is also an inhibitor of attractive molecular properties with good potency in HCV subgenomic replication trials and suitable for clinical candidates.

JTK-853 is a novel, non-nucleoside inhibitor of Hepatitis C Virus (HCV) polymerase, exhibiting effective antiviral activity in HCV replicon cells with EC50s of 0.38 μM for genotype 1a H77 strain and 0.035 μM for genotype 1b Con1 strain.

Beclabuvir is an allosteric inhibitor that binds to thumb site 1 of the HCV NS5B RNA-dependent RNA polymerase, inhibiting recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 (IC50 < 28 nM).

TMC-649128, a RNA polymerase NS5B inhibitor, is used for the treatment of HCV infection.

Beclabuvir, also known as BMS-791325, is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. B

Galidesivir triphosphate is a substrate for viral RNA-dependent RNA polymerase (RDRP), resulting in termination of viral RNA replication and thus serves as an antiviral. Galidesivir triphosphate inhibits HCV NS5B RNA polymerase activity and protects mice against Ebola. Galidesivir triphosphate (Immucillin-A triphosphate) is converted by the prodrug Galidesivir.

Cis-Lomibuvir (cis-VX-222), a cis-isomer of Lomibuvir, is a selective non-nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase (RdRp), targeting thumb pocket 2 with a dissociation constant (Kd) of 17 nM. It exhibits an EC50 of 5.2 nM against the 1b/Con1 HCV subgenomic replicon, demonstrating a preference for inhibiting elongative RNA synthesis over de novo-initiated RNA synthesis.

GSK5852 (GSK2485852) is an HCV NS5B RdRp polymerase inhibitor, inhibiting NS5B with an IC50 of 50 nM. It exhibits antiviral effects against the hepatitis C virus (HCV) with EC50 values of 3.0 nM for GT1a and 1.7 nM for GT1b.

Balapiravir (R1626, Ro 4588161) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). IC50 Value: Target: HCV Balapiravir was discontinued for safety reasons in 28-36% of patients (m

ABT-072, also known as potassium trihydrate, is a highly effective non-nucleoside inhibitor of the HCV NS5B polymerase, administered orally. This compound exhibits potent activity against HCV GT1a (with an EC50 of 1 nM) and HCV GT1b (with an EC50 of 0.3 nM).

6-Hydroxypyridin-3-ylboronic acid is a heterocyclic building block.1,2It has been used in the synthesis of non-nucleoside inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B).16-Hydroxypyridin-3-ylboronic acid has also been used in the synthesis of mammalian target of rapamycin (mTOR) inhibitors.2 1.Hendricks, R.T., Spencer, S.R., Blake, J.F., et al.3-Hydroxyisoquinolines as inhibitors of HCV NS5b RNA-dependent RNA polymeraseBioorg. Med. Chem. Lett.19(2)410-414(2009) 2.Verheijen, J.C., Richard, D.J., Curran, K., et al.Discovery of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as highly potent and sselective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): Optimization of the 6-aryl substituentJ. Med. Chem.52(24)8010-8024(2009)

Azvudine hydrochloride (RO-0622) is a potent nucleoside reverse transcriptase inhibitor (NRTI) with strong antiviral effects against HIV, HBV, and HCV. It demonstrates highly potent inhibition of HIV-1 (EC50 ranging from 0.03 to 6.92 nM) and HIV-2 (EC50 ranging from 0.018 to 0.025 nM), and effectively inhibits NRTI-resistant viral strains.

Deleobuvir sodium is the salt form of Deleobuvir, also known as BI207127, a non-nucleoside hepatitis C virus NS5B polymerase inhibitor for the treatment of hepatitis C. Deleobuvir was tested in combination regimens with pegylated interferon and ribavirin, and in interferon-free regimens with other direct-acting antiviral agents including faldaprevir. Deleobuvir showed that a triple combination of deleobuvir, faldaprevir, and ribavirin performed well in HCV genotype 1b patients. Efficacy fell below 50%, however, for dual regimens without ribavirin and for genotype 1a patients. In December 2013, deleobuvir was discontinued since recent findings from phase III trials did not suggest sufficient efficacy.

HCV-086, a RNA-directed RNA polymerase (NS5B) inhibitor, is used for the treatment of HCV infection.

VCH-916 is a new nonnucleoside inhibitor of HCV NS5B polymerase.

Ribavirin-13C5is intended for use as an internal standard for the quantification of ribavirin by GC- or LC-MS. Ribavirin is an antiviral guanosine nucleoside analog.1,2Upon entry into cells, ribavirin is metabolized to an active triphosphate form that induces viral RNA chain termination and inhibits viral polymerases. It reduces replication in a panel of seven RNA and four DNA viruses in Vero cells (EC50s = 2-95 μg/ml).3Ribavirin also reduces replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero cells (EC50= 109.5 μM).4Aerosol administration of ribavirin (30 mg/kg) reduces mortality in a mouse model of influenza A infection.5Formulations containing ribavirin have been used in the treatment of respiratory syncytial virus (RSV), hepatitis C virus (HCV), and viral hemorrhagic fevers. 1.Gilbert, B.E., and Knight, V.Biochemistry and clinical applications of ribavirinAntimicrob. Agents Chemother.30(2)201-205(1986) 2.Gordon, C.J., Tchesnokov, E.P., Woolner, E., et al.Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potencyJ. Biol. Chem.295(20)6785-6797(2020) 3.Kirsi, J.J., North, J.A., McKernan, P.A., et al.Broad-spectrum antiviral activity of 2-β-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agentAntimicrob. Agents Chemother.24(3)353-361(1983) 4.Wang, M., Cao, R., Zhang, L., et al.Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Res.30(3)269-271(2020) 5.Wilson, S.Z., Knight, V., Wyde, P.R., et al.Amantadine and ribavirin aerosol treatment of influenza A and B infection in miceAntimicrob. Agents Chemother.17(4)642-648(1980)

Lomibuvir (VCH-222) is a selective, non-nucleoside allosteric inhibitor of HCV NS5B polymerase (RdRp) with a Kd of 17 nM. Lomibuvir inhibits the 1b Con1 HCV subgenomic replicon with an EC 50 of 5.2 nM. Lomibuvir preferentially inhibits elongative RNA synthesis rather than de novo -initiated RNA synthesis [1].

GSK-625433, a homochiral inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, has the ability to inhibit the polymerase of both HCV genotypes 1a and 1b.

PSI-353661 (GS-558093), a purine nucleotide NS5B polymerase inhibitor, is effective against HCV infection, displaying EC90 values of 8 nM and 11 nM for wild-type and S282T resistant HCV replicons, respectively. It is capable of generating high concentrations of the active triphosphate form in primary human hepatocytes [1] [3].

Dasabuvir (ABT-333) sodium is a non-nucleoside hepatitis C virus (HCV) polymerase inhibitor that exhibits inhibition of the RNA-dependent RNA polymerase (RNA polymerase) encoded by the HCV NS5B gene. Dasabuvir sodium inhibited genotype 1a (strain H77) replicon (EC50: 7.7 nM) and 1b (strain Con1) replicon (EC50: 1.8 nM).

AL-611 is an HCV NS5B polymerase inhibitor (EC50 = 5 nM).

Tegobuvir (GS 333126) is a specific and covalent HCV NS5B polymerase inhibitor.

PSI-6206 13CD3 is the deuterium labeled PSI-6206. PSI-6206 is a potent and selective HCV NS5B polymerase inhibitor.