7BAK

Crystal structure of SARS-CoV-2 main protease treated with ebselen

7BAK の概要

• エントリーDOI: 10.2210/pdb7bak/pdb
• 分子名称: Main Protease, SELENIUM ATOM (3 entities in total)
• 機能のキーワード: sars-cov-2, main protease, covid19, ebselen, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33904.51

構造登録者

Amporndanai, K.,O'Neill, P.M.,Hasnain, S.S. (登録日: 2020-12-15, 公開日: 2021-06-02, 最終更新日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.05 Å)