Hepatitis C virus NS3 protease-helicase (HCV NS3 (or NS3/4A when described with its essential cofactor))

Hepatitis C virus NS3 protease-helicase is a bifunctional viral enzyme essential for the life cycle of hepatitis C virus. The N-terminal one-third of NS3 has serine protease activity, which cleaves the HCV polyprotein into its functional components with the assistance of the NS4A cofactor, while the C-terminal two-thirds functions as an RNA helicase and NTPase, unwinding RNA structures necessary for viral replication[1][2][3][4]. NS3 is the primary target for several direct-acting antivirals (including boceprevir, telaprevir, grazoprevir, glecaprevir, voxilaprevir), which bind the protease domain and inhibit viral maturation[4]. The helicase domain is less exploited clinically but is of rising interest for antiviral development[3]. The NS3 protease-helicase is considered highly druggable due to its essentiality for replication, unique structure among viral and host enzymes, and has been structurally characterized for structure-based drug design[4].

Other names

NS3 proteinNS3/4A protease (when including the NS4A cofactor)HCV NS3 protease-helicaseHCV NS3

Direct-acting antiviral agents (DAAs) inhibit the serine protease active site, blocking polyprotein cleavage needed for viral replication[4]. Some agents bind reversibly covalently to the protease; others use large noncovalent surface interactions[4]. Experimental inhibitors targeting the helicase and the NTPase activity (preclinical)[3][4].