7BAJ

Crystal structure of ligand-free SARS-CoV-2 main protease

Summary for 7BAJ

• Entry DOI: 10.2210/pdb7baj/pdb
• Descriptor: Main Protease (2 entities in total)
• Functional Keywords: sars-cov-2, main protease, covid19, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 33825.55

Authors

Amporndanai, K.,O'Neill, P.M.,Hasnain, S.S. (deposition date: 2020-12-15, release date: 2021-06-02, Last modification date: 2024-01-31)

Primary citation

Amporndanai, K.,Meng, X.,Shang, W.,Jin, Z.,Rogers, M.,Zhao, Y.,Rao, Z.,Liu, Z.J.,Yang, H.,Zhang, L.,O'Neill, P.M.,Samar Hasnain, S.
Inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives.
Nat Commun, 12:3061-3061, 2021

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

PubMed: 34031399
DOI: 10.1038/s41467-021-23313-7

Experimental method

X-RAY DIFFRACTION (1.65 Å)