2. Academic Validation
  3. Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CLpro covalent inhibitors

Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CLpro covalent inhibitors

  • Eur J Med Chem. 2022 Feb 5;229:114046. doi: 10.1016/j.ejmech.2021.114046.
Julia K Stille 1,  Jevgenijs Tjutrins 1,  Guanyu Wang 1,  Felipe A Venegas 1,  Christopher Hennecker 1,  Andrés M Rueda 1,  Itai Sharon 2,  Nicole Blaine 1,  Caitlin E Miron 1,  Sharon Pinus 1,  Anne Labarre 1,  Jessica Plescia 1,  Mihai Burai Patrascu 1,  Xiaocong Zhang 1,  Alexander S Wahba 1,  Danielle Vlaho 1,  Mitchell J Huot 1,  T Martin Schmeing 2,  Anthony K Mittermaier 3,  Nicolas Moitessier 4
Affiliations

Affiliations

  • 1 Department of Chemistry, McGill University, 801 Sherbrooke St W, Montreal, QC, Canada, H3A 0B8.
  • 2 Department of Biochemistry, McGill University, 3649 Promenade Sir William Osler Montreal, QC, Canada, H3G 0B1.
  • 3 Department of Chemistry, McGill University, 801 Sherbrooke St W, Montreal, QC, Canada, H3A 0B8. Electronic address: anthony.mittermaier@mcgill.ca.
  • 4 Department of Chemistry, McGill University, 801 Sherbrooke St W, Montreal, QC, Canada, H3A 0B8. Electronic address: nicolas.moitessier@mcgill.ca.
PMID: 34995923 DOI: 10.1016/j.ejmech.2021.114046
Abstract

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for Antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro (main coronaviruses cysteine-protease) has been identified as a promising target for the development of Antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

Keywords

3CLpro; Mpro; SARS-CoV2; covalent inhibitors.

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