HCV Inhibitor

EIDD-2749 (4'-Fluorouridine) is an orally active RdRp inhibitor. EIDD-2749 effectively blocks the replication of RSV and SARS-CoV-2. EIDD-2749 also exhibits activity against HCV and lymphocytic choriomeningitis virus (LCMV). EIDD-2749 is a promising oral therapeutic candidate for COVID-19 and is also suitable for research on other RNA viruses.

Glecaprevir is a novel HCV NS3/4A protease inhibitor, with IC₅₀ values ranging from 3.5 to 11.3 nM. Glecaprevir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 4.09 μM.

Ledipasvir (GS-5885) is an inhibitor of the hepatitis C virus NS5A, with EC₅₀s of 34 pM and 4 pM against genotype 1a and 1b replicon, respectively. Ledipasvir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.62 μM.

Velpatasvir (VEL, GS-5816) is a novel pan-genotypic hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor with activity against genotype 1 (GT1) to GT6 HCV replicons. Velpatasvir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 2.16 μM.

Paritaprevir (ABT-450) is a potent, orally active and antiviral non-structural protein 3/4A (NS3/4A) protease inhibitor with EC₅₀s of 1 and 0.21 nM against HCV 1a and 1b, respectively. Paritaprevir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.31 μM. Paritaprevir is metabolized primarily by cytochrome P450 (CYP) 3A. The plasma concentration and half-life of Paritaprevir can be enhanced by Ritonavir (a CYP450 inhibitor).

Gentiopicroside, a naturally occurring iridoid glycoside, inhibits P450 activity, with an IC₅₀ and a K_i of 61 μM and 22.8 μM for CYP2A6; Gentiopicroside has anti-inflammatoryand antioxidative effects.

Mizoribine (NSC 289637), an imidazole nucleoside, inhibits HCV RNA replication with IC₅₀ of approximately 100 μM for anti-HCV activity. Immunosuppressant. Mizoribine, an IMPDH inhibitor, inhibits replication of SARS-CoV with IC₅₀s of 3.5 μg/mL and 16 μg/mL for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, respectively.

Telaprevir (VX-950) is a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, the steady-state inhibitory constant (K_i) of Telaprevir is 7 nM against a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide. Telaprevir inhibits SARS-CoV-2 3CL^pro activity.

Grazoprevir potassium salt (MK-5172 potassium salt) is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with K_is of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively. Grazoprevir potassium salt inhibits SARS-CoV-2 3CL^pro activity.

Vesatolimod (GS-9620) is a potent, selective and orally active agonist of Toll-Like Receptor (TLR7) with an EC₅₀ of 291 nM.

Merimepodib (VX-497) is a noncompetitive and oral inhibitor of inosine monophosphate dehydrogenase (IMPDH) with broad spectrum antiviral activities.

YM-53601, a squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in vivo. YM-53601 inhibits squalene synthase derived from human hepatoma cells with an IC₅₀ of 79 nM. Lipid-lowering agent. YM-53601 is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) enzyme activity and abrogates HCV propagation.

Daclatasvir (BMS-790052) is a potent and orally active HCV NS5A protein inhibitor with EC₅₀s range of 9-146 pM for multiple HCV replicon genotypes. Daclatasvir is also a organic anion transporting polypeptide 1B (OATP1B) and OATP1B3 inhibitor with IC₅₀s of 1.5 µM and 3.27 µM, respectively.

GS-443902 trisodium (GS-441524 triphosphate trisodium) is a potent viral RNA-dependent RNA-polymerases (RdRp) inhibitor with IC₅₀s of 1.1 μM, 5 μM for RSV RdRp and HCV RdRp, respectively. GS-443902 trisodium is the active triphosphate metabolite of Remdesivir (GS-5734).

Pibrentasvir is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with EC₅₀s ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6.

Bicyclol (SY801) is an orally active derivative of the traditional Chinese medicine Schisandra chinensis, which has antiviral, anti-inflammatory, immunomodulatory, antioxidant, anti-steatosis, anti-fibrotic and anti-tumor activities. Bicyclol regulates the expression of heat shock proteins and plays an anti-apoptosis role in hepatocytes. Bicyclol reduces the activation of NF-κB and the levels of inflammatory factors in hepatocytes infected with hepatitis C virus (HCV) by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and prevents ferroptosis in acute liver injury. Bicyclol can change the expression of Mdr-1, GSH/GST and Bcl-2, increase the intracellular concentration of anticancer drugs, and sensitize drug-resistant cells to anticancer drugs. Bicyclol inhibits the proliferation of human malignant hepatoma cells by regulating the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway. Bicyclol can be used in the study of chronic hepatitis, acute liver injury, nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma.

Alisporivir (Debio-025) is a cyclophilin inhibitor molecule with potent anti-hepatitis C virus (HCV) activity.

Dasabuvir (ABT-333) is a nonnucleoside hepatitis C virus (HCV) polymerase inhibitor. Dasabuvir inhibits RNA-dependent RNA polymerase encoded by the HCV NS5B gene. Dasabuvir inhibits genotype 1a (strain H77) and 1b (strain Con1) replicons, with EC₅₀ values of 7.7 and 1.8 nM, respectively.

Danoprevir (ITMN-191) is an orally active NS3/4A protease inhibitor for hepatitis C virus (HCV) with an IC₅₀ of 0.29 nM and is selective for NS3/4A over a panel of 53 proteases (IC₅₀ higher than 10 μM). Danoprevir (ITMN-191) inhibits HCV genotypes 1a, 1b, 4, 5, and 6 (IC₅₀s=0.2-0.4 nM) as well as 2b and 3a (IC₅₀s=1.6, 3.5 nM). Danoprevir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 0.05 μM.

2'-O-Methylcytidine is an orally active 2'-substituted nucleoside as a inhibitor of HCV replication with antiviral activity. 2'-O-Methylcytidine inhibits RNA-dependent RNA polymerase (NS5B)-catalyzed RNA synthesis in vitro, in a manner that is competitive with substrate nucleoside triphosphate.