HCV Protease Inhibitor

Asunaprevir (BMS-650032) is a potent and orally bioavailable hepatitis C virus (HCV) NS3 protease inhibitor, with IC₅₀ of 0.2 nM-3.5 nM. Asunaprevir inhibits SARS-CoV-2 3CL^pro activity.

Grazoprevir (MK-5172) 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 inhibits SARS-CoV-2 3CL^pro activity.

Simeprevir (TMC435; TMC435350) is an oral, potent and highly specific hepatitis C virus (HCV) NS3/4A protease inhibitor with a K_i of 0.36 nM. Simeprevir inhibits HCV replication with an EC₅₀ of 7.8 nM. Simeprevir also potently suppresses SARS-CoV-2 replication and synergizes with Remdesivir. Simeprevir inhibits the main protease (M^pro) and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, and also modulates host immune responses.

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.

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).

BI-1388 is a macrocyclic acylsulfonamide-based HCV NS3-4A protease inhibitor. BI-1388 inhibits clinically relevant drug-resistant mutant strains (KRAS^D168V gt 1b and KRAS^R155K gt 1a) and exhibits high liver distribution. BI-1388 is applicable for the research of HCV infection.

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.

Voxilaprevir (GS-9857) is a noncovalent, reversible inhibitor of HCV NS3/4A protease inhibitor (PI) with pangenotypic antiviral activity. Voxilaprevir inhibits genotype 1b and 3a wild-type NS3 proteases with K_i values of 0.038 nM and 0.066 nM, respectively. Voxilaprevir is an orally active direct-acting antiviral agent (DAA) and can be used for HCV infection research.

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.

Clemizole hydrochloride is an H1 histamine receptor antagonist, is found to substantially inhibit HCV replication. Clemizole hydrochloride is an inhibitor of TRPC5 channel. The IC₅₀ of Clemizole hydrochloride for RNA binding by NS4B is 24 nM, whereas its EC₅₀ for viral replication is 8 μM.

Boceprevir (EBP 520) is a potent, highly selective, orally bioavailable HCV NS3 protease inhibitor with a K_i of 14 nM in both enzyme assay and an EC₉₀ of 350 nM in cell-based replicon assay. Boceprevir inhibits SARS-CoV-2 3CL^pro activity.

Narlaprevir (SCH 900518) is a selective and orally bioavailable NS3 protease inhibitor with a K_i value of 6 nM and an EC₉₀ value of 40 nM. Narlaprevir also inhibits the HCV nonstructural protein 3 serine protease. Narlaprevir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 2.3 μM.

Grazoprevir hydrate (MK-5172 hydrate) 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 hydrate inhibits SARS-CoV-2 3CL^pro activity.

Pheophytin a is a multi-target inhibitor, anticancer agent, antioxidant and antiviral agent. Pheophytin a directly binds to and inhibits HCV-NS3/4A protease (IC₅₀=0.89 μM) to block viral replication. Pheophytin a also scavenges free radicals, reduces ferric ions, and exhibits cytotoxic activity against breast cancer cells. Pheophytin a effectively inhibits LPS-induced production of nitric oxide, prostaglandin E2, NOS2 and COX-2, as well as various pro-inflammatory cytokines, by downregulating the transcription levels of inflammatory mediators and blocking the ERK1/2 and STAT-1 pathways. In a low nerve growth factor environment, Pheophytin a also enhances ERK1/2 phosphorylation and synergistically promotes neurite outgrowth through MAPK pathway. Pheophytin a can be used to investigate the pathogenic mechanisms of diseases including chronic hepatitis C, sepsis, breast cancer and Alzheimer's disease.

ITMN 4077 is a macrocyclic inhibitor against Hepatitis C Virus (HCV) NS3 protease (EC₅₀: 2131 nM).

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

Coblopasvir (KW-136) dihydrochloride is a pangenotypic non-structural protein 5A (NS5A) inhibitor. Coblopasvir dihydrochloride can be used for research of chronic hepatitis C virus infection.

Valopicitabine (NM283) dihydrochloride is a nucleoside analog and the orally bioavailable proagent of the potent anti-HCV agent 2'-C-methylcytidine (NM107). NM107competitively inhibits NS5B polymerase, causing chain termination.

Mellein ((R)-Mellein) is an isocoumarin compound with antibacterial activity. Mellein inhibits the activity of HCV Protease, disrupts the cell wall of Xanthomonas sp., and acts as an insect trail pheromone. Mellein is applicable to research related to fungal infections, bacterial infections, and hepatitis C virus infections.