7P51

CRYSTAL STRUCTURE OF THE SARS-COV-2 MAIN PROTEASE COMPLEXED WITH FRAGMENT F01

7P51 の概要

• エントリーDOI: 10.2210/pdb7p51/pdb
• 関連するPDBエントリー: 7NTS 7NTT
• 分子名称: 3C-like proteinase, SODIUM ION, DIMETHYL SULFOXIDE, ... (5 entities in total)
• 機能のキーワード: 3clpro, main protease, sars-cov-2, 2019-ncov, inhibitor, viral protein
• 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: 1
• 化学式量合計: 34346.51

構造登録者

Hanoulle, X.,Moschidi, D. (登録日: 2021-07-13, 公開日: 2021-10-06, 最終更新日: 2024-11-20)

主引用文献

Cantrelle, F.X.,Boll, E.,Brier, L.,Moschidi, D.,Belouzard, S.,Landry, V.,Leroux, F.,Dewitte, F.,Landrieu, I.,Dubuisson, J.,Deprez, B.,Charton, J.,Hanoulle, X.
NMR Spectroscopy of the Main Protease of SARS-CoV-2 and Fragment-Based Screening Identify Three Protein Hotspots and an Antiviral Fragment.
Angew.Chem.Int.Ed.Engl., 60:25428-25435, 2021

PubMed Abstract: The main protease (3CLp) of the SARS-CoV-2, the causative agent for the COVID-19 pandemic, is one of the main targets for drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. The deciphering of these mechanisms is a crucial step to enable the search for inhibitors. In this context, using NMR spectroscopy, we studied the conformation of dimeric 3CLp from the SARS-CoV-2 and monitored ligand binding, based on NMR signal assignments. We performed a fragment-based screening that led to the identification of 38 fragment hits. Their binding sites showed three hotspots on 3CLp, two in the substrate binding pocket and one at the dimer interface. F01 is a non-covalent inhibitor of the 3CLp and has antiviral activity in SARS-CoV-2 infected cells. This study sheds light on the complex structure-function relationships of 3CLp and constitutes a strong basis to assist in developing potent 3CLp inhibitors.

PubMed: 34570415
DOI: 10.1002/anie.202109965

実験手法

X-RAY DIFFRACTION (1.474 Å)