Science 368, 779–782 (2020)

Cell https://doi.org/10.1016/j.cell.2020.05.034 (2020)

The coronavirus SARS-CoV-2 is responsible for the disease COVID-19, which has become a global pandemic. The SARS-CoV-2 structural protein Spike and the non-structural protein RNA-dependent RNA polymerase (nsp12) are potential drug targets given their importance in host-cell recognition and viral replication, respectively. To further understand the mechanism of viral polymerase activity, Gao et al. solved the cryo-EM structure of SARS-CoV-2 nsp12 with cofactors nsp7 and nsp8, components of the polymerase processivity clamp. Although the overall architecture is similar to that of the closely related SARS-CoV-1 homolog, the authors noted differences in the nucleotidyltransferase (NiRAN) domain and the existence of an N-terminal β-hairpin that stabilizes the overall structure by insertion into the groove clamped by the NiRAN domain and the palm subdomain of the polymerase domain. Catalytic complex structures from Wang et al. showed structural rearrangements required to accommodate the RNA, and a pre-translocated complex with the nucleotide analog remdesivir clarified the transition of the polymerase primase complex to its catalytic complex. These findings can potentially enable development of new antiviral drugs against a promising target.

Credit: Zihe Rao