HCV replicon

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

2'-C-Methyladenosine is an inhibitor of hepatitis C virus (HCV) replication and a ribonucleoside diphosphate reductase inhibitor from Corynebacterium renalis. It inhibits HCV replicon and NS5B-catalyzed RNA synthesis with IC50 values of 0.3 μM and 1.9 μM, respectively. Additionally, 2'-C-Methyladenosine inhibits LRV1 in Leishmania guyanensis (Lgy) and Leishmania braziliensis.

Furaprofen is an orally available, selective and potent HCV inhibitor with anti-inflammatory activity, inhibits carrageenan-induced paw edema in rats and inhibits cotton pellet-induced granulomas in rats at higher doses.

Daclatasvir dihydrochloride (BMS-790052 dihydrochloride) is an orally available antiviral agent that inhibits the NS5A region of the hepatitis C virus (HCV) and is used in combination with other oral antivirals to treat chronic hepatitis C. Elevations in serum enzyme levels during daclatasvir therapy are uncommon, and it has not been convincingly implicated in cases of clinically apparent liver injury with jaundice.

Velpatasvir (GS-5816), also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.

2'-O-Methylcytidine is a nucleoside derivative and an inhibitor of hepatitis C virus (HCV) non-structural protein 5B (NS5B; IC50= 3.8 μM).1It inhibits HCV replication in a replicon assay (IC50= 21.2 μM). 1.Migliaccio, G., Tomassini, J.E., Carroll, S.S., et al.Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitroJ. Bio. Chem.278(49)49164-49170(2003)

RO8191 (CDM-3008) (CDM-3008) is an agonist of interferon (IFN) receptor.

Boceprevir (SCH 503034) is a novel, potent, highly selective, orally bioavailable HCV NS3 protease inhibitor with Ki of 14 nM in both enzyme assay and EC90 of 350 nM in cell-based replicon assay.

Daclatasvir (EBP 883) (BMS-790052) is a highly selective inhibitor of HCV NS5A with EC50 of 9-50 pM, for a broad range of HCV replicon genotypes and the JFH-1 genotype 2a infectious virus in cell culture. Phase 3.

ITMN4077 has antiviral activity against Hepatitis C virus infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication with an EC50 of 2.131μM.

Sofosbuvir D6 is the deuterium labeled Sofosbuvir. Sofosbuvir is an active inhibitor of HCV RNA replication in the HCV replicon assay, demonstrates potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity B is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay, with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity C is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity D is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

Sofosbuvir impurity E is the less active impurity of Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay,with potent anti-hepatitis C virus (HCV) activity.

Inarigivir soproxil (SB9200) is an agonist of innate immunity that demonstrates effective antiviral activity against resistant hepatitis C virus (HCV) variants, with EC50s of 2.2 and 1.0 μM for HCV 1a 1b in cells of genotype 1 HCV replicon systems.

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.

MK-0608 is an orally bioavailable HCV replication inhibitor in vitro(EC50 = 0.3 μM and EC90=1.3 μM in the subgenomic-replicon assay).

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.

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).

HCV-IN-39 (Compound 18a) is a potent, orally active nucleoside inhibitor of hepatitis C virus (HCV), effective against the GT1a replicon (EC50: 0.259 μM), GT1b replicon (EC50: 0.434 μM), and GT1b CES1 replicon (EC50: 0.069 μM).

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].

BMS-824 is a potent NS5A inhibitor. The 50% inhibition of HCV replicon replication for BMS-824 was approximately 5 nM, with a therapeutic index of >10,000. BMS-824 showed good specificity for HCV, as it was not active against several other RNA and DNA viruses.

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.