Inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives

• DOI: 10.1038/s41467-021-23313-7
• Publication Date: 2021-05-24T10:02:53Z
• Authors: Kangsa Amporndanai; Xiaoli Meng; Weijuan Shang; Zhenmig Jin; Michael Rogers; Yao Zhao; Zihe Rao; Zhi-Jie Liu; Haitao Yang; Leike Zhang; Paul M. O’Neill; S. Samar Hasnain
• Keywords: Ebselen; Cysteine protease

Abstract The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. main protease of (M pro ), critical for viral replication, is a key target therapeutic development. An organoselenium drug called ebselen been demonstrated have potent M inhibition and antiviral activity. We examined the binding modes its derivative in via high resolution co-crystallography investigated their chemical reactivity mass spectrometry. Stronger than ability rescue infected cells were observed number derivatives. A free selenium atom bound with cysteine catalytic dyad revealed crystallographic structures MR6-31-2 suggesting hydrolysis enzyme covalent adduct formation phenolic by-product, confirmed by engagement selenation mechanism suggests wider applications these compounds against other zoonotic beta -corona viruses.