SARS-CoV RNA-dependent RNA Polymerase (RdRp)

The SARS-CoV RNA-dependent RNA polymerase (RdRp), also known as non-structural protein 12 (nsp12), is a central enzyme in the replication and transcription machinery of coronaviruses, including both SARS-CoV and SARS-CoV-2. It catalyzes the synthesis of viral RNA from an RNA template, a process essential for viral genome replication and subgenomic mRNA production. The core structure of RdRp consists of a canonical "right-hand" architecture with three main subdomains: fingers, palm, and thumb. It also features an N-terminal Nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain, and a unique β-hairpin domain at its N terminus. For full enzymatic activity, nsp12 forms a complex with two cofactors: nsp7 and nsp8. RdRp is indispensable for replication of the full-length viral genome and transcription of subgenomic RNAs. By enabling rapid amplification of the coronavirus genome inside infected cells, RdRp is critical for productive infection. Due to its essential role in virus replication—and absence from human cells—RdRp is a prime target for antiviral drug development. Several inhibitors have been studied, including Remdesivir, Favipiravir, and Sorafenib.

Other names

Non-structural protein 12nsp12SARS-CoV-2 RdRp

Inhibition of viral RNA synthesis by various mechanisms, including chain termination and interference with enzymatic activity.