9PUH

SARS-CoV-2 Papain-like Protease (PLpro) in complex with Fragment 11

これはPDB形式変換不可エントリーです。

9PUH の概要

• エントリーDOI: 10.2210/pdb9puh/pdb
• 分子名称: Papain-like protease nsp3, 1'-methylspiro[[1]benzopyran-2,4'-piperidin]-4(3H)-one, ZINC ION, ... (4 entities in total)
• 機能のキーワード: viral protease, inhibitor, 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: 3
• 化学式量合計: 108429.81

構造登録者

Taylor, A.J.,Zhao, B.,Fesik, S.W. (登録日: 2025-07-31, 公開日: 2026-01-21, 最終更新日: 2026-02-04)

主引用文献

Wei, Q.,Taylor, A.J.,Barmade, M.A.,Teuscher, K.B.,Chowdhury, S.,Apakama, C.,Anderson-Daniels, J.,Yongqing, Z.,Schultz, D.C.,Rietz, T.A.,South, T.M.,Crow, M.M.,Zhao, B.,Amporndanai, K.,Sensintaffar, J.L.,Phan, J.,Cherry, S.,Denison, M.,Lee, T.,Fesik, S.W.
Discovery of Fragment-Based Inhibitors of SARS-CoV-2 PL Pro .
J.Med.Chem., 69:1419-1433, 2026

PubMed Abstract: SARS-CoV-2 papain-like protease (PL) plays a key role in viral replication and the host immune response and is a promising target for developing new antiviral treatments. We previously reported a fragment-based screen to identify hits that bind to SARS-CoV-2 PL. Here, we describe the discovery of potent PL inhibitors by optimizing one of these hits via extensive medicinal chemistry guided by multiple X-ray structures of cocomplexes. Lead compound is shown to bind to the S3 and S4 pockets with nanomolar affinity (0.4 μM) and exhibits robust cellular activity and resistance to mutation. This novel class of PL inhibitors can potentially be used as a starting point for the development of inhibitors to combat the emergence of drug-resistant viral strains and future coronavirus outbreaks.

PubMed: 41521555
DOI: 10.1021/acs.jmedchem.5c02832

実験手法

X-RAY DIFFRACTION (2.39 Å)