replicon

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)

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.

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.

Antiviral agent 17 (Compound 4) is an anti-infection compound with strong antiviral effects, demonstrated by an EC50 of 0.015 μM in a human replicon assay, and effective against murine norovirus. It has potential applications in studying infectious and malignant diseases[1].

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.

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.

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.

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.

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.

HCV-IN-31 is a HCV inhibitor with an EC50/EC95 of 15.7 μM.

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.

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.

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.

DBPR-110 is a nonstructural protein 5A (NS5A) inhibitor. DBPR-110 reduced the reporter expression of the HCV1b replicon with a EC(50) and a selective index value of 3.9 ± 0.9 pM and >12,800,000, respectively. DBPR-110 reduced HCV2a replicon activity with

YKL-04-085 is a potent inhibitor of viral translation. YKL-04-085 has cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation. YKL-04-085 demonstrated good inhibition of translation of the DENV2(GVD) r

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.

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.

Ledipasvir hydrochloride (GS-5885) is a hepatitis C virus NS5A inhibitor, demonstrating potent activity with EC50 values of 34 pM for genotype 1a replicon and 4 pM for genotype 1b replicon. It also functions as a SARS-CoV 3CL pro inhibitor with an IC50 of 1.62 µM [3].

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.

FR171456 is a natural specific inhibitor of mammalian nsdhl and yeast erg26p, inhibiting an artificial hepatitis c viral replicon, and showung broad antifungal 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.

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).

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.

R-1479 (4'-Azidocytidine) is an RdRp inhibitor with an IC50 value of 1.28 μM for HCV RNA replication in the HCV subgenomic replicon system.

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.

Ledipasvir (GS-5885) is a Hepatitis C Virus NS5A Inhibitor. The mechanism of action of ledipasvir is as a P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor.

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).

Ledipasvir D-tartrate with EC50 values of 34 pM against GT1a and 4 pM against GT1b replicon. is an inhibitor of the hepatitis C virus NS5A.

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 13CD3 is the deuterium labeled Sofosbuvir. Sofosbuvir is an active HCV RNA replication inhibitor in the HCV replicon assay, with potent anti-hepatitis C virus (HCV) activity.

Narlaprevir is an effective, selective, and orally bioavailable NS3 protease inhibitor(Ki=6 nM; EC90=40 nM).

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].

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.

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).