Viral RNA-dependent RNA polymerase and host inosine monophosphate dehydrogenase (RdRp/IMPDH)

The target complex known as the viral RNA replication machinery involves both the viral RNA-dependent RNA polymerase (RdRp) and the host enzyme inosine monophosphate dehydrogenase (IMPDH). RdRp is the primary enzyme responsible for the replication and transcription of the viral RNA genome, making it a cornerstone of the viral life cycle (Source: PubMed, PMID: 25666762). IMPDH is a host-cell enzyme that catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides, which are required as substrates for RNA synthesis (Source: UniProt, P12268). Drugs such as ribavirin exert their antiviral effects by targeting both components: they inhibit IMPDH to starve the virus of GTP and act as mutagenic substrates for RdRp to induce error catastrophe in the viral population (Source: StatPearls, NBK513243). This dual-targeting strategy is employed to treat a variety of RNA virus infections, including Hepatitis C and certain viral hemorrhagic fevers. However, the involvement of host enzymes like IMPDH often results in significant clinical toxicities, most notably dose-limiting hemolytic anemia and potential teratogenic effects.

Other names

RNA replication machineryViral RdRpHost IMPDHInosine-5'-monophosphate dehydrogenase

Dual mechanism involving the inhibition of host inosine monophosphate dehydrogenase (IMPDH) to deplete intracellular GTP pools and the direct inhibition or lethal mutagenesis of viral RNA-dependent RNA polymerase (RdRp) by nucleoside triphosphate analogs.