1. Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL pro covalent inhibitors.
- Author
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Stille JK, Tjutrins J, Wang G, Venegas FA, Hennecker C, Rueda AM, Sharon I, Blaine N, Miron CE, Pinus S, Labarre A, Plescia J, Burai Patrascu M, Zhang X, Wahba AS, Vlaho D, Huot MJ, Schmeing TM, Mittermaier AK, and Moitessier N
- Subjects
- Animals, Drug Design, High-Throughput Screening Assays, Humans, Virus Replication drug effects, Antiviral Agents chemical synthesis, Antiviral Agents pharmacology, Coronavirus 3C Proteases antagonists & inhibitors, Protease Inhibitors chemical synthesis, Protease Inhibitors pharmacology, COVID-19 Drug Treatment
- 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, 3CL
pro (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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)- Published
- 2022
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