8HUT

Crystal structure of MERS main protease in complex with S217622

8HUT の概要

• エントリーDOI: 10.2210/pdb8hut/pdb
• 分子名称: ORF1a, 6-[(6-chloranyl-2-methyl-indazol-5-yl)amino]-3-[(1-methyl-1,2,4-triazol-3-yl)methyl]-1-[[2,4,5-tris(fluoranyl)phenyl]methyl]-1,3,5-triazine-2,4-dione (3 entities in total)
• 機能のキーワード: viral protein-inhibitor complex, viral protein
• 由来する生物種: Middle East respiratory syndrome-related coronavirus (MERS-CoV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66504.56

構造登録者

Lin, C.,Zhang, J.,Li, J. (登録日: 2022-12-24, 公開日: 2023-06-21, 最終更新日: 2024-02-07)

主引用文献

Lin, C.,Jiang, H.,Li, W.,Zeng, P.,Zhou, X.,Zhang, J.,Li, J.
Structural basis for the inhibition of coronaviral main proteases by ensitrelvir.
Structure, 31:1016-1024.e3, 2023

PubMed Abstract: Main protease (M) is a highly conserved cysteine protease that plays a vital role in the replication of coronaviruses, making it an attractive pan-coronaviral therapeutic target. Ensitrelvir (S-217622), developed by Shionogi, is the first orally active non-covalent, non-peptidic SARS-CoV-2 M inhibitor, which also displays antiviral efficacy against other human coronaviruses as well as SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). Here, we report the crystal structures of the main proteases from SARS-CoV-2, SARS-CoV-2 VOC/VOIs, SARS-CoV, MERS-CoV, and HCoV-NL63 bound to the inhibitor S-217622. A detailed analysis of these structures illuminates key structural determinants essential for inhibition and elucidates the binding modes of the main proteases from different coronaviruses. Given the importance of the main protease for the treatment of coronaviral infection, structural insights obtained from this study could accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.

PubMed: 37421945
DOI: 10.1016/j.str.2023.06.010

実験手法

X-RAY DIFFRACTION (1.98 Å)