7NTQ

Crystal structure of the SARS-CoV-2 Main Protease complexed with N-(pyridin-3-ylmethyl)thioformamide

7NTQ の概要

• エントリーDOI: 10.2210/pdb7ntq/pdb
• 関連するPDBエントリー: 7NTS 7NTT 7NTW
• 分子名称: 3C-like proteinase, N-(pyridin-3-ylmethyl)thioformamide, SODIUM ION, ... (6 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: 34759.57

構造登録者

Dupre, E.,Villeret, V.,Hanoulle, X. (登録日: 2021-03-10, 公開日: 2022-03-02, 最終更新日: 2024-11-20)

主引用文献

Brier, L.,Hassan, H.,Hanoulle, X.,Landry, V.,Moschidi, D.,Desmarets, L.,Rouille, Y.,Dumont, J.,Herledan, A.,Warenghem, S.,Piveteau, C.,Carre, P.,Ikherbane, S.,Cantrelle, F.X.,Dupre, E.,Dubuisson, J.,Belouzard, S.,Leroux, F.,Deprez, B.,Charton, J.
Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses.
Eur.J.Med.Chem., 250:115186-115186, 2023

PubMed Abstract: Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CL) and the papain-like protease, to generate non-structural proteins essential for the virus life cycle. Both proteases are recognized as promising drug targets for the development of anti-coronavirus chemotherapy. Aiming at identifying broad spectrum agents for the treatment of COVID-19 but also to fight emergent coronaviruses, we focused on 3CL that is well conserved within this viral family. Here we present a high-throughput screening of more than 89,000 small molecules that led to the identification of a new chemotype, potent inhibitor of the SARS-CoV-2 3CL. The mechanism of inhibition, the interaction with the protease using NMR and X-Ray, the specificity against host cysteine proteases and promising antiviral properties in cells are reported.

PubMed: 36796300
DOI: 10.1016/j.ejmech.2023.115186

実験手法

X-RAY DIFFRACTION (1.495 Å)