Hepatitis C virus NS3-NS4A protease (HCV NS3-NS4A protease (sometimes written as HCV NS3/4A protease))

The **Hepatitis C virus NS3-NS4A protease** is a membrane-associated, multifunctional viral enzyme complex essential for the replication of hepatitis C virus (HCV). The complex consists of the NS3 protein, which has both an N-terminal serine protease domain (amino acids 1–180) and a C-terminal RNA helicase domain, and the cofactor NS4A, an 11-amino-acid peptide crucial for optimal folding and activity of the protease[3]. The protease cleaves the HCV polyprotein at specific sites (3–4A, 4A4B, 4B5A, 5A5B), enabling production of viral nonstructural proteins necessary for replication. Additionally, NS3-NS4A protease cleaves key adaptor proteins in the host innate immune signaling pathways (such as MAVS and TRIF), allowing the virus to evade the immune response[1][2][3]. The essential role of this enzyme in both viral replication and immune evasion makes it a validated target for antiviral drugs, and several direct-acting antivirals (DAAs) have been developed to inhibit this protease, significantly improving treatment outcomes for chronic HCV infection[2][4][6].

Other names

NS3/4A proteaseHCV proteaseHepatitis C virus NS3-4A proteaseNS3/4A serine protease

Reversible or irreversible inhibition of the NS3-NS4A serine protease active site, blocking polyprotein processing[2][4][6]. Inhibition of viral RNA replication[2][6]. Restoration of host innate antiviral signaling (by preventing cleavage of host proteins such as MAVS and TRIF)[6].