8JOP

Crystal structure of the SARS-CoV-2 main protease in complex with 11a

8JOP の概要

• エントリーDOI: 10.2210/pdb8jop/pdb
• 分子名称: 3C-like proteinase nsp5, methyl (6~{R})-5-ethanoyl-7-oxidanylidene-6-[4-(trifluoromethyl)phenyl]-8,9,10,11-tetrahydro-6~{H}-benzo[b][1,4]benzodiazepine-2-carboxylate (3 entities in total)
• 機能のキーワード: severe acute respiratory syndrome coronavirus 2, main protease, viral protein
• 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: 34283.98

構造登録者

Zeng, R.,Liu, Y.Z.,Wang, F.L.,Yang, S.Y.,Lei, J. (登録日: 2023-06-08, 公開日: 2023-08-16, 最終更新日: 2024-11-13)

主引用文献

Wang, F.,Zeng, R.,Qiao, J.,Xia, A.,Li, Y.,Li, F.,Wu, Y.,Liu, Y.,Zhao, X.,Lei, J.,Yang, S.
Discovery of benzodiazepine derivatives as a new class of covalent inhibitors of SARS-CoV-2 main protease.
Bioorg.Med.Chem.Lett., 92:129407-129407, 2023

PubMed Abstract: The COVID-19 pandemic has caused people immense suffering all over the world. Although the World Health Organization (WHO) has announced the end of the pandemic, the sporadic virus epidemic is still ongoing and may exist permanently. Effective antivirals against SARS-CoV-2 are important to deal with the long-term threat. The main protease (M) is a crucial target for drug development due to its role in the process of virus's replication and transcription. Herein, we report benzodiazepine derivatives as a new class of M inhibitors. Structure-activity relationship (SAR) studies led to the discovery of the most active compound, methyl 10-(2-chloroacetyl)-1-oxo-11-(4-(trifluoromethyl)phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-diazepine-7-carboxylate (11a), which shows an IC value of 0.180 ± 0.004 μM. The X-ray crystal structure shows that 11a covalently binds to M. Collectively, we have obtained a new small molecule inhibitor targeting M, which can serve as a lead compound for subsequent drug discovery against SARS-CoV-2.

PubMed: 37437852
DOI: 10.1016/j.bmcl.2023.129407

実験手法

X-RAY DIFFRACTION (2.7 Å)