A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease. Academic Article uri icon

abstract

  • As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (MPro) for pathogenesis and replication. During crystallographic analyses of MPro crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of MPro, a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more open active site that can potentially be targeted for the development of novel SARS-CoV-2 antivirals. The structural rearrangement of MPro by this cross-link indicates that small molecules that lock MPro in the cross-linked form can potentially be used with other active-site-targeting molecules such as paxlovid for synergistic effects in inhibiting SARS-CoV-2 viral replication.

published proceedings

  • ACS Chem Biol

altmetric score

  • 2.5

author list (cited authors)

  • Yang, K. S., Blankenship, L. R., Kuo, S., Sheng, Y. J., Li, P., Fierke, C. A., ... Liu, W. R.

citation count

  • 1

complete list of authors

  • Yang, Kai S||Blankenship, Lauren R||Kuo, Syuan-Ting Alex||Sheng, Yan J||Li, Pingwei||Fierke, Carol A||Russell, David H||Yan, Xin||Xu, Shiqing||Liu, Wenshe Ray

publication date

  • March 2023