Hepatitis C virus nonstructural protein 3–nonstructural protein 4A complex (HCV NS3–NS4A)

The **Hepatitis C virus nonstructural protein 3–nonstructural protein 4A complex (NS3–NS4A)** consists of two viral proteins essential for HCV replication. NS3 contains a serine protease domain and an RNA helicase domain, while NS4A serves as a cofactor that stabilizes NS3 and tethers the complex to intracellular membranes. The NS3–NS4A complex cleaves the HCV polyprotein at specific sites, enabling production of other viral nonstructural proteins, and it also impairs the host innate immune response by cleaving mitochondrial antiviral signaling protein (MAVS), thereby inhibiting interferon induction[1][2][3]. Direct-acting antivirals targeting NS3–NS4A protease are a cornerstone of HCV therapy and act by preventing proper viral protein processing and replication[2][3]. Resistance mutations and drug–drug interactions are main therapeutic challenges.

Other names

NS3/4A proteaseHCV NS3–NS4A serine proteaseNS3/NS4A complex

Inhibition of NS3–NS4A serine protease activity, blocking cleavage of the viral polyprotein and formation of mature viral proteins Restoration of host innate immune signaling by preventing NS3–NS4A-mediated MAVS cleavage