Hepatitis C virus nonstructural protein 3–5B (HCV NS3–NS5B)

Hepatitis C virus nonstructural proteins NS3–NS5B are virally encoded enzymes and regulatory proteins that play essential roles in the replication cycle of hepatitis C virus (HCV), a positive-sense single-stranded RNA virus. NS3 functions as both a serine protease—critical for cleaving the viral polyprotein into functional units—and as an RNA helicase/NTPase, required for unwinding RNA during genome replication. NS5B is the viral RNA-dependent RNA polymerase, directly responsible for synthesizing new copies of the viral genome. NS4A acts as a cofactor for NS3, NS4B organizes replication complex assembly on altered host membranes, and NS5A is a phosphoprotein coordinating replication and virion assembly[1][4][5]. Together, NS3–NS5B constitute the main "replication module" (replicase) of HCV, forming a membrane-associated multiprotein complex essential for viral RNA synthesis and persistence. As such, NS3, NS5A, and NS5B are all validated therapeutic targets for direct-acting antiviral drugs, which have revolutionized hepatitis C therapy by specifically inhibiting these proteins and thereby blocking viral replication and cure infection in most patients[1][4][5][7].

Other names

HCV NS3 proteinHCV NS4A proteinHCV NS4B proteinHCV NS5A proteinHCV NS5B proteinHepatitis C virus replicase complexHCV replicase module

Inhibition of NS3/4A protease blocks viral polyprotein processing and replication; Inhibition of NS5A disrupts replication complex assembly and viral RNA replication; Inhibition of NS5B RNA-dependent RNA polymerase prevents new viral RNA synthesis