Voxilaprevir

Voxilaprevir (GS-9857) is a noncovalent, reversible inhibitor of HCV NS3/4A protease inhibitor (PI) with pangenotypic antiviral activity^[1]. Voxilaprevir inhibits genotype 1b and 3a wild-type NS3 proteases with K_i values of 0.038 nM and 0.066 nM, respectively^[1]. Voxilaprevir is an orally active direct-acting antiviral agent (DAA) and can be used for HCV infection research^[2]. IC50 & Target: Hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease^[1] In Vitro: NS3/4A protease is essential for proteolytic cleavage of the HCV encoded polyprotein (intomature forms of NS3, NS4A, NS4B, NS5A and NS5B proteins) and hence for viral replication^[1].
In enzymatic assays using recombinant NS3 protease domains and isogenic NS4A peptide cofactors provided in trans. Voxilaprevir is against HCV genotype 1b and 3a NS3 proteases with K_i values of 0.038 nM and 0.066 nM, respectively^[1].
In stable cell lines (Huh-7-Lunet or Huh7-1C cells) expressing renilla luciferase-encoding HCV replicons. Voxilaprevir exhibits potent pangenotypic antiviral activity with EC₅₀ ranging from 0.33 to 6.6 nM across genotypes 1 to 6. Voxilaprevir is against HCV replicon strain DQ314805, H77, Con1, JFH-1, J6,J8 (full length) and HM568433, SA13 (NS3 Chimera) with IC₅₀ values of 0.33 nM, 3.9 nM, 3.3 nM, 3.7 nM, 4.5 nM, 1.8 nM, and 6.6 nM, 1.9 nM, respectively^[1].