Discovery of Non-Covalent Inhibitors Targeting the SARS-CoV-2 Main Protease (UA21-099)

This technology encompasses the development of novel inhibitors for the main protease, or Mpro, of SARS-CoV-2. The main protease of SARS-CoV-2 is a validated drug target and could be key to the development of more antiviral drugs against the virus. The inhibitors proposed in this technology are notable, as they are non-covalent inhibitors with high enzymatic inhibition and antiviral activity against SARS-CoV-2. Background: The COVID-19 pandemic caused by the SARS-CoV-2 virus has brought forth an urgent need for novel drugs and therapeutics to help fight the novel disease. Demand for an effective and safe antiviral drug has been extremely high throughout the pandemic. One possible drug target that various researchers have identified is the main protease or “Mpro” of the SARS-CoV-2. The main protease is key to the viral life-cycle, as it allows for the virus to make functional viral proteins. The majority of current antiviral drugs target the SARS-CoV-2 main protease by covalent modification of a cysteine residue by reactive warhead. This technology proposes and tests two inhibitors that inhibit the same protease, but do so non-covalently. Even when compared to another existing non-covalent inhibitor, the two compounds proposed by this technology showed increased enzymatic inhibition, stronger affinity, and significant antiviral ability in cell culture. Learn more at http://bit.ly/UA21-099 Anne Spieth annes@tla.arizona.edu 520-626-1577

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