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

ABSTRACT: The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M^pro), critical for viral replication, is a key target for therapeutic development. An organoselenium drug called ebselen has been demonstrated to have potent M^pro inhibition and antiviral activity. We have examined the binding modes of ebselen and its derivative in M^pro via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger M^pro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. A free selenium atom bound with cysteine of catalytic dyad has been revealed in crystallographic structures of M^pro with ebselen and

SUBMITTER: Amporndanai K 

PROVIDER: S-EPMC8144557 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature