biostudies-literatureUnknown229Stille JKSevere 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 3CL^pro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL^pro. 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.European journal of medicinal chemistry114046https://www.ebi.ac.uk/biostudies/studies/S-EPMC8665847biostudies-literatureDesign, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL^pro covalent inhibitors.PMC8665847Burai Patrascu MPinus SMittermaier AKPlescia JSharon IWang GHennecker CRueda AMMiron CEHuot MJTjutrins JLabarre AStille JKZhang XBlaine NVenegas FAWahba ASVlaho DMoitessier NSchmeing TMfalseDesign, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL^pro covalent inhibitors.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 3CL^pro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL^pro. 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.2022-01-01T00:00:00Z2022 Feb2024-11-06T18:31:52.892Z2022-02-11T16:16:42.624ZS-EPMC86658473499592310.1016/j.ejmech.2021.114046