Coronavirus RNA-dependent RNA polymerase (RdRp)

Coronavirus RNA-dependent RNA polymerase (RdRp), frequently termed nsp12, is the essential polymerase enzyme responsible for replicating and transcribing the large, single-stranded, positive-sense RNA genomes of coronaviruses such as SARS-CoV-2. RdRp operates within a multi-protein complex (including cofactors nsp7 and nsp8) and catalyzes the synthesis of viral RNA using an RNA template, enabling the virus to produce both its genomic RNA and subgenomic mRNAs necessary for protein production. The enzyme features conserved structural domains and motifs that are targeted by antiviral agents such as remdesivir and molnupiravir. Owing to its central role in viral proliferation and its sequence conservation across coronaviruses, RdRp has garnered significant attention as a prime therapeutic target for drug development, particularly in response to the COVID-19 pandemic. Inhibitors typically mimic natural nucleotides, are incorporated into nascent RNA, and disrupt viral replication by inducing chain termination or lethal mutagenesis. Resistance and safety challenges persist, but the polymerase remains one of the most promising viral drug targets.

Other names

RNA-dependent RNA polymerase (RdRp)Non-structural protein 12 (nsp12)SARS-CoV-2 RdRpViral RdRp

Nucleoside/nucleotide analogs act as chain terminators or mutagenic agents incorporated by RdRp, halting viral RNA synthesis. Remdesivir: Delayed chain termination after incorporation into viral RNA. Molnupiravir: Induces lethal mutagenesis by incorporation into viral RNA. Favipiravir: Similar nucleoside analog mechanism. Direct inhibition of polymerase catalytic activity