Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors

Abstract

Severe diseases such\nas the ongoing COVID-19 pandemic, as well as the previous SARS and MERS\noutbreaks, are the result of coronavirus infections and have demonstrated the\nurgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral\nreplication and function, 3CLpro has been identified as a promising\ntarget for the development of antiviral drugs. \nPreviously reported SARS-CoV 3CLpro non-covalent inhibitors\nwere used as a starting point for the development of covalent inhibitors of\nSARS-CoV-2 3CLpro. We report herein our efforts in design and\nsynthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease\nwas used as a screening platform.