Viral RNA-dependent RNA polymerase (RdRp) (RdRp)

Viral RNA-dependent RNA polymerase (RdRp) is the central catalytic component of the viral replication machinery in RNA viruses, excluding retroviruses (Source: Nature Reviews Microbiology, 2022). It is responsible for synthesizing new RNA genomes and transcribing viral mRNA from an RNA template, a process essential for viral proliferation (Source: UniProt, 2024). The enzyme often functions as part of a larger replication-transcription complex (RTC) that includes other viral proteins such as helicases, exonucleases, and primases (Source: Cell, 2020). Because RdRp has no direct functional equivalent in human cells, it is a highly attractive target for broad-spectrum antiviral drugs (Source: Journal of Biological Chemistry, 2021). Most clinical inhibitors are nucleoside or nucleotide analogs that act as pro-drugs, which, once phosphorylated by host kinases, compete with natural nucleotides for incorporation into the nascent RNA strand, leading to chain termination (Source: NIH, 2023). Other agents, like Molnupiravir, induce an error catastrophe by causing excessive mutations during replication (Source: FDA, 2021). However, the high error rate of RdRp itself facilitates the rapid development of resistance mutations, posing a significant challenge for long-term efficacy (Source: Lancet Infectious Diseases, 2022).

Other names

RNA replicaseRNA-directed RNA polymeraseRdRp complexReplication-transcription complexViral replication machinery

Inhibition of viral RNA synthesis through competitive binding as nucleoside or nucleotide analogs, leading to premature chain termination or lethal mutagenesis (Source: Nature Reviews Drug Discovery, 2021).