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Publication Abstract from PubMed

As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M(Pro)) for pathogenesis and replication. During crystallographic analyses of M(Pro) 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 M(Pro), 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 M(Pro) by this cross-link indicates that small molecules that lock M(Pro) 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.

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.,Yang KS, Blankenship LR, Kuo SA, Sheng YJ, Li P, Fierke CA, Russell DH, Yan X, Xu S, Liu WR ACS Chem Biol. 2023 Mar 17;18(3):449-455. doi: 10.1021/acschembio.2c00695. Epub , 2023 Jan 11. PMID:36629751^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.