Hepatitis C virus non-structural protein 5 (NS5)

Hepatitis C virus non-structural protein 5 (NS5) is a large precursor protein within the HCV polyprotein that is post-translationally cleaved by the NS3/4A protease into two distinct functional units: NS5A and NS5B (UniProt, PubMed) [6, 14]. NS5A is a multifunctional phosphoprotein essential for viral RNA replication and virion assembly, acting as a scaffold for the replication complex and interacting with various host factors (PubMed, PMC) [1, 3, 13]. NS5B is the viral RNA-dependent RNA polymerase (RdRp), responsible for synthesizing the viral RNA genome (UniProt, Hepatitis C Online) [5, 12]. Both proteins are critical targets for direct-acting antivirals (DAAs); NS5A inhibitors (e.g., ledipasvir) disrupt the assembly and replication complex, while NS5B inhibitors (e.g., sofosbuvir) block polymerase activity (PubMed, PMC) [2, 4, 10]. Targeting these components of the NS5 precursor has revolutionized HCV treatment, leading to high cure rates across multiple genotypes (PubMed) [10, 12].

Other names

NS5NS5 polyproteinNS5 precursorNon-structural protein 5

Inhibition of viral RNA replication and assembly through targeting the NS5A phosphoprotein (disrupting replication complex formation and virion assembly) and the NS5B RNA-dependent RNA polymerase (chain termination or allosteric inhibition).