Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2023

Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses

Résumé

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 (3CLpro) 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 3CLpro 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 3CLpro. 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.

Dates et versions

hal-04020216 , version 1 (08-03-2023)

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Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, et al.. Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses. European Journal of Medicinal Chemistry, 2023, 250, pp.115186. ⟨10.1016/j.ejmech.2023.115186⟩. ⟨hal-04020216⟩
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