9BRV

SARS-CoV-2 Papain-like Protease (PLpro) with Fragment 5

これはPDB形式変換不可エントリーです。

9BRV の概要

• エントリーDOI: 10.2210/pdb9brv/pdb
• 分子名称: Papain-like protease nsp3, N-[2-(dimethylamino)ethyl]-N'-(3-methylphenyl)thiourea, ZINC ION, ... (6 entities in total)
• 機能のキーワード: plpro, sars-cov-2, drug discovery, inhibitor, viral protein, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73482.88

構造登録者

Amporndanai, K.,Zhao, B.,Fesik, S.W. (登録日: 2024-05-11, 公開日: 2024-07-31, 最終更新日: 2024-09-04)

主引用文献

Taylor, A.J.,Amporndanai, K.,Rietz, T.A.,Zhao, B.,Thiruvaipati, A.,Wei, Q.,South, T.M.,Crow, M.M.,Apakama, C.,Sensintaffar, J.L.,Phan, J.,Lee, T.,Fesik, S.W.
Fragment-Based Screen of SARS-CoV-2 Papain-like Protease (PL pro ).
Acs Med.Chem.Lett., 15:1351-1357, 2024

PubMed Abstract: Coronaviruses have been responsible for numerous viral outbreaks in the past two decades due to the high transmission rate of this family of viruses. The deadliest outbreak is the recent Covid-19 pandemic, which resulted in over 7 million deaths worldwide. SARS-CoV-2 papain-like protease (PL) plays a key role in both viral replication and host immune suppression and is highly conserved across the coronavirus family, making it an ideal drug target. Herein we describe a fragment-based screen against PL using protein-observed NMR experiments, identifying 77 hit fragments. Analyses of NMR perturbation patterns and X-ray cocrystallized structures reveal fragments bind to two distinct regions of the protein. Importantly none of the fragments identified belong to the same chemical class as the few reported inhibitors, allowing for the discovery of a novel class of PL inhibitors.

PubMed: 39140055
DOI: 10.1021/acsmedchemlett.4c00238

実験手法

X-RAY DIFFRACTION (2.6 Å)