8HQI

Crystal structure of SARS-Cov-2 main protease P132H mutant in complex with inhibitor YH-53

8HQI の概要

• エントリーDOI: 10.2210/pdb8hqi/pdb
• 分子名称: 3C-like proteinase nsp5, N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-1-oxidanylidene-3-[(3S)-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-4-methoxy-1H-indole-2-carboxamide (3 entities in total)
• 機能のキーワード: viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67471.03

構造登録者

Li, W.W.,Zhang, J.,Li, J. (登録日: 2022-12-13, 公開日: 2023-12-20, 最終更新日: 2025-01-01)

主引用文献

Luo, J.,Wang, W.,Jiang, H.,Li, W.,Zeng, P.,Wang, J.,Zhou, X.,Zou, X.,Chen, S.,Wang, Q.,Zhang, J.,Li, J.
Crystal structures of main proteases of SARS-CoV-2 variants bound to a benzothiazole-based inhibitor.
Acta Biochim.Biophys.Sin., 55:1257-1264, 2023

PubMed Abstract: Main protease (M ) serves as an indispensable factor in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as its constantly emerging variants and is therefore considered an attractive target for antiviral drug development. Benzothiazole-based inhibitors targeting M have recently been investigated by several groups and proven to be promising leads for coronaviral drug development. In the present study, we determine the crystal structures of a benzothiazole-based inhibitor, YH-53, bound to M mutants from SARS-CoV-2 variants of concern (VOCs) or variants of interest (VOIs), including K90R (Beta, B.1.351), G15S (Lambda, C.37), Y54C (Delta, AY.4), M49I (Omicron, BA.5) and P132H (Omicron, B.1.1.529). The structures show that the benzothiazole group in YH-53 forms a C-S covalent bond with the sulfur atom of catalytic residue Cys145 in SARS-CoV-2 M mutants. Structural analysis reveals the key molecular determinants necessary for interaction and illustrates the binding mode of YH-53 to these mutant M s. In conclusion, structural insights from this study offer more information to develop benzothiazole-based drugs that are broader spectrum, more effective and safer.

PubMed: 37357528
DOI: 10.3724/abbs.2023053

実験手法

X-RAY DIFFRACTION (1.55 Å)