Poster Presentation 49th Lorne Conference on Protein Structure and Function 2024

A structural analysis of the nsp9 proteins from the coronaviruses SARS CoV-2 and MERS CoV reveals a conserved RNA binding interface (#413)

Serene El-Kamand 1 , Gayathri Mani 1 , Bing Wang 2 , Mar-Dean Du Plessis 1 , David L Baker 1 , Derek J Richard 3 , Irina Artsimovitch 2 , Ann H Kwan 4 , Liza Cubeddu 1 , Roland Gamsjaeger 1
  1. Western Sydney University, Penrith, NSW, Australia
  2. The Ohio State University, Ohio, Columbus, USA
  3. Queensland University of Technology, Woolloongabba, QLD, Australia
  4. University of Sydney, Sydney, NSW, Australia

Middle East respiratory syndrome coronavirus (MERS CoV) and severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) are RNA viruses from the Betacoronavirus family that cause serious respiratory illness in humans. One of the conserved non-structural proteins encoded for by the coronavirus family is non-structural protein 9 (nsp9). Nsp9 plays an important role in the RNA capping process of the viral genome, where it is covalently linked to viral RNA (known as RNAylation) by the conserved viral polymerase, nsp12. Nsp9 also directly binds to RNA; in our recently published study we reveal a distinct RNA recognition interface in the SARS CoV-2 nsp9 by using a combination of nuclear magnetic resonance (NMR) spectroscopy and biolayer interferometry (BLI). In a follow-up study, we have utilised a similar methodology to determine a structural model of RNA binding of the related MERS CoV. Based on these data, we uncover important similarities and differences to SARS CoV-2 nsp9 and other coronavirus nsp9 proteins. Our findings will significantly contribute to the ongoing global efforts to develop novel drugs against these highly contagious SARS and MERS viruses.