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

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is comprised of a large single stranded positive polarity RNA genome that acts as messenger RNA after entering the host. Post infection, the ssRNA encodes two open reading frames, produced through host ribosomal frameshifting that transcribes two polyprotein products. The polyprotein products are subsequently cleaved into 27 viral proteins by internally encoded proteases. Further processing of the polyprotein releases an RNA-polymerase along with several non-structural proteins that facilitate RNA synthesis and may play a role in the enveloping process but are not included in the viral coat. Treatment of infections caused by betacoronoaviruses have focused on three therapeutic strategies; vaccination with the spike glycoprotein of the SARS-Cov-2 envelope (Wrapp et al., 2020) , and small-molecule targeting of conserved viral enzymes (e.g. the Mpro protease (Zhenming et al. 2020 ) (Yang et al., 2005) and the RNApolymerase (Yan et al. 2020) . Nevertheless, some of the betacoronaviral non-structural proteins appear important for viral replication within SARS-CoV and influence pathogenesis (Frieman et al., 2012) . Despite their close homology between viruses, such non-structural proteins remain of interest as they may have conserved roles within the viral lifecycle of SARS-CoV-2.