Hepatitis C virus nonstructural protein 3-4A serine protease (NS3-4A)

The Hepatitis C virus nonstructural protein 3-4A serine protease (NS3-4A or NS3/4A) is a membrane-associated, multifunctional enzyme essential for viral replication and maturation. It forms a non-covalent heterodimer composed of the catalytically active N-terminal portion of the NS3 protein and the NS4A cofactor. NS3-4A cleaves the hepatitis C viral polyprotein at four specific sites, generating mature nonstructural proteins (NS3, NS4A, NS4B, NS5A, and NS5B) required for assembly of the viral replication complex. In addition to proteolytic processing, NS3-4A plays a direct role in immune evasion by cleaving host cell proteins involved in antiviral signaling, notably MAVS and TRIF, thereby blocking induction of type I interferon responses. NS3-4A is a validated and clinically exploited antiviral drug target, with several approved direct-acting antiviral drugs that specifically inhibit its activity, leading to effective cure of hepatitis C infection[1][2][3][6].

Other names

NS3/4ANS3-NS4A proteaseHCV NS3-4AHCV NS3/4A protease

Inhibition of viral protease activity (drugs competitively and/or covalently inhibit the serine protease catalytic site, blocking viral polyprotein processing and halting viral replication)