Telaprevir

The antiviral agent telaprevir is a covalent, reversible inhibitor of hepatitis C virus (HCV) nonstructural protease 3/4A (NS3/4A; Ki = 7nM), a serine protease that is essential for viral replication by cleaving the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B, leading to inhibition of viral polyprotein processing and subsequently decrease of viral RNA replication. It inhibits viral replication in genotype 1b HCV replicon cells (IC50 = 354nM) and isolated human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC50 = 280nM).Used in stabilizable polypeptide linkages (StaPLs) chemogenetic platform, for pharmacological regulation of protein expression/function. StaPL sequences can be engineered into target proteins rendering them functional only in the presence of telaprevir.Telaprevir has been identified as a potential inhibitor of SARS-CoV-2, responsible for COVID-19. It inhibits SARS-CoV-2 viral replication by targeting the viral 3C-like Protease (3CLpro), interacting through hydrogen bond formation with Ser46 and Gln182 main chain amines as well as Glu166 α-carboxyl group.