7TUU

Structure of the SARS-CoV-2 main protease in complex with halicin

7TUU の概要

• エントリーDOI: 10.2210/pdb7tuu/pdb
• 分子名称: 3C-like proteinase nsp5, 5-nitro-1,3-thiazole (3 entities in total)
• 機能のキーワード: main protease, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34215.92

構造登録者

Yang, K.S.,Liu, W.R. (登録日: 2022-02-03, 公開日: 2022-08-03, 最終更新日: 2024-11-20)

主引用文献

Yang, K.S.,Alex Kuo, S.T.,Blankenship, L.R.,Geng, Z.Z.,Li, S.G.,Russell, D.H.,Yan, X.,Xu, S.,Liu, W.R.
Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease.
Curr Res Chem Biol, 2:100025-100025, 2022

PubMed Abstract: The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (M), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with M. The potency test shows that halicin inhibits the activity of M an IC of 181.7 ​nM. Native mass spectrometry and X-ray crystallography studies clearly indicate that the nitrothiazole fragment of halicin covalently binds to the catalytic cysteine C145 of M. Interaction and conformational changes inside the active site of M suggest a favorable nucleophilic aromatic substitution reaction mechanism between M C145 and halicin, explaining the high inhibition potency of halicin towards M.

PubMed: 35815070
DOI: 10.1016/j.crchbi.2022.100025

実験手法

X-RAY DIFFRACTION (1.85 Å)