7NTQ

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

Summary for 7NTQ

• Entry DOI: 10.2210/pdb7ntq/pdb
• Related: 7NTS 7NTT 7NTW
• Descriptor: 3C-like proteinase, N-(pyridin-3-ylmethyl)thioformamide, SODIUM ION, ... (6 entities in total)
• Functional Keywords: 3clpro, main protease, sars-cov-2, 2019-ncov, inhibitor, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 1
• Total formula weight: 34759.57

Authors

Dupre, E.,Villeret, V.,Hanoulle, X. (deposition date: 2021-03-10, release date: 2022-03-02, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.495 Å)