NMR Spectroscopy reveals that the Nsp8 N-terminal domain, a key component of the viral RNA-dependent RNA polymerase, is capable of folding and binding RNA without other replicase components..

The SARS Cov-2 Nsp8 protein is a key part of the RNA replicase, as its N-terminal domain (NTD) anchors RNA, Nsp12 and Nsp13. While its CTD is well resolved, the conformation of the NTD is unclear as it is predicted to be disordered and, when studied by X-ray crystallography and cryo-EM, adopts a variety of complex-dependent conformations or is partly invisible. Using NMR spectroscopy, we show that the Nsp8 NTD possesses two long alpha-helices that fold independently followed by a progressively disordered tail whose folding would require interaction with other replicase components of SARS CoV-2. This less structured tail contributes to binding dsRNA. These results are published in Nuc. Acid Res. https://doi.org/10.1093/nar/gkad714