Biological Efficacy of 40 Noncovalent SARS-CoV-2 Main Protease Inhibitors: A Computational Study

The COVID-19 crisis caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the world to accelerate many drugs and vaccines for emergency use. Several inhibitors with the potent enzymatic inhibition and cellular antiviral activity are reported to target the main protease (Mpro) of SARS-CoV-2. We selected ML188 and its 39 analogs to study the physicochemical properties and biological efficacy of these inhibitors. Results showed that these inhibitors are highly stable and chemically active. With good bioavailability, none of the inhibitors showed poor intestinal absorption. Few toxicity related issues, high Gastrointestinal (GI) absorption and no Blood-brain barrier (BBB) activity is seen in most of the inhibitors. The involvement of these inhibitors with multitargets indicated their potential usage for drug repurposing.