SARS-CoV-2 RNA-directed RNA polymerase (nsp12) (RdRp)

The SARS-CoV-2 RNA-directed RNA polymerase (RdRp), primarily composed of the nsp12 protein, is the catalytic core of the viral replication-transcription complex (UniProt P0DTD1). It is responsible for synthesizing the viral genome and subgenomic mRNAs, a process essential for the production of new virions within the host cell (Hillen et al., 2020, Nature). Because RdRp is highly conserved across the Coronaviridae family, its conserved epitopes are primary targets for broad-spectrum antiviral drugs and T-cell-based vaccines (Grifoni et al., 2020, Cell). Small-molecule inhibitors like remdesivir act as adenosine analogs that cause delayed chain termination during RNA synthesis (Yin et al., 2020, Science). Other agents, such as molnupiravir, induce lethal mutagenesis, leading to the accumulation of errors that render the virus non-functional (Kabinger et al., 2021, Nature Structural & Molecular Biology). The high conservation of these epitopes makes them ideal for therapeutic strategies aiming to minimize the impact of viral variants and ensure long-term efficacy of treatments.

Other names

nsp12Non-structural protein 12SARS-CoV-2 RdRpRNA-dependent RNA polymeraseSARS-CoV-2 PolRdRp conserved epitopes

Inhibition of viral RNA synthesis through delayed chain termination or the induction of lethal mutagenesis via nucleoside analog incorporation.