Fast and Effective Prediction of the Absolute Binding Free Energies of Covalent Inhibitors of SARS-CoV-2 Main Protease and 20S Proteasome.

ABSTRACT: The COVID-19 pandemic has been a public health emergency with continuously evolving deadly variants around the globe. Among many preventive and therapeutic strategies, the design of covalent inhibitors targeting the main protease (M^pro) of SARS-CoV-2 that causes COVID-19 has been one of the hotly pursued areas. Currently, about 30% of marketed drugs that target enzymes are covalent inhibitors. Such inhibitors have been shown in recent years to have many advantages that counteract past reservation of their potential off-target activities, which can be minimized by modulation of the electrophilic warhead and simultaneous optimization of nearby noncovalent interactions. This process can be greatly accelerated by exploration of binding affinities using computational models, which ar

SUBMITTER: Zhou J 

PROVIDER: S-EPMC9359807 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature