Hepatitis C Virus Nonstructural Protein 3 (NS3)

Hepatitis C virus nonstructural protein 3 (NS3) is a multifunctional viral protein essential for the life cycle of the hepatitis C virus (HCV). It is produced as a 70 kDa cleavage product from the HCV polyprotein and plays critical roles in viral replication, polyprotein processing, and immune evasion. It contains a N-terminal serine protease domain responsible for cleaving the nonstructural region of the HCV polyprotein and a C-terminal helicase/NTPase domain, which functions as an RNA helicase and nucleoside triphosphatase, unwinding RNA during genome replication and assembly. NS3 requires association with its cofactor, nonstructural protein 4A (NS4A), to achieve full enzymatic activity. Several direct acting antivirals—such as boceprevir, telaprevir, paritaprevir—specifically inhibit NS3/4A protease activity.

Inhibition of NS3/4A protease activity