Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9

Dene Littler; Benjamin Gully; Rhys N Colson; Jamie Rossjohn

At this stage it is unclear whether the bound residues within our structure have any bearing on the physiological function of Nsp9COV19. In the first instance this would seem unlikely, however our sequence is that of a rhinoviral 3C protease site and the SARS-CoV main protease cleaves consensus sequences following an LQ sequence (Zhu et al., 2011) . The bound 3C-LE residues have hallmarks of the LQ motif and are proximal to the highly conserved GxxxG motif. There are no obvious structural features to preclude, or select for, a Glu to Gln substitution within our . CC-BY-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.28.013920 doi: bioRxiv preprint bound sequence. Notably the M pro cleavage sequence occurs at multiple points throughout the CoV genome as the majority of viral proteins are released by its activity, thus it remains possible that Nsp9 may associate with unprocessed viral polyproteins retaining them near the viral RNA. Within our structure Met-101 provides contacts with the bound valine sidechain but the presence of Asn-33 nearby may also accommodate residues such as lysine at this position. Peptide-binding assays will need to be developed to rigorously assess such possibilities.