Viral RNA-dependent RNA polymerase and Inosine-5'-monophosphate dehydrogenase (RdRp and IMPDH)

Viral RNA-dependent RNA polymerase (RdRp) is an enzyme found in most RNA viruses that enables the replication and transcription of viral RNA genomes from an RNA template. RdRp is essential for the life cycle of RNA viruses and is characterized by a conserved catalytic core formed by palm, fingers, and thumb subdomains, resembling a closed right-hand structure. It is the key enzymatic target for direct-acting antivirals against many RNA viruses. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a host enzyme that catalyzes the rate-limiting step in de novo guanine nucleotide biosynthesis. It is not a viral protein, but some broad-spectrum antivirals (e.g., Ribavirin) act in part by inhibiting host IMPDH, depleting GTP pools critical for viral RNA synthesis. Note: The combination of "Viral RNA-dependent RNA polymerase and host IMPDH" as a single target is not standard. These are two separate proteins, with distinct roles and drug targeting rationales; combining them is often used in broad antiviral screening, but for structured target records, should be split into "Viral RNA-dependent RNA polymerase" and "Inosine-5'-monophosphate dehydrogenase" individually.

Other names

RNA-dependent RNA polymerase (for viral target)RNA replicase (for viral target)IMP dehydrogenase (for host target)

RdRp: Competitive inhibition of nucleotide incorporation, chain termination, or mutagenesis of viral RNA (Remdesivir, Favipiravir, Ribavirin). IMPDH: Inhibition of conversion of inosine monophosphate to xanthosine monophosphate, reducing guanine nucleotide pool and impairing viral replication (Ribavirin, Mycophenolate).