Hepatitis C virus replication complex and host nucleotide biosynthetic pathways (HCV-RC/Host-NTP)

The Hepatitis C virus (HCV) replication machinery is a multi-protein complex composed of non-structural viral proteins (NS3, NS4A, NS4B, NS5A, and NS5B) that assemble on host intracellular membranes to facilitate viral RNA synthesis. This machinery relies heavily on host nucleotide biosynthetic pathways to maintain a sufficient pool of ribonucleoside triphosphates (NTPs) required for rapid viral genome replication. Key viral components include the NS3/4A serine protease, which processes the viral polyprotein, and the NS5B RNA-dependent RNA polymerase, which serves as the catalytic core for RNA production. Host factors, such as Inosine monophosphate dehydrogenase (IMPDH), are often exploited by the virus to boost guanosine triphosphate (GTP) levels, making them secondary therapeutic targets. Modern Direct-Acting Antivirals (DAAs) specifically target these viral enzymes to achieve high cure rates, while older adjunct therapies like Ribavirin modulate host nucleotide pools to exert antiviral pressure.

Other names

HCV replication machineryHCV replicase complexHost nucleotide metabolism in HCV infectionHCV non-structural protein complex

Inhibition of viral NS3/4A protease, NS5A phosphoprotein, or NS5B RNA-dependent RNA polymerase; depletion of intracellular GTP pools via IMPDH inhibition.