The catalytic reaction in SARS-CoV-2 main protease is activated by a proton transfer (PT) from Cys145 to His41. same PT likely also required for the covalent binding of some inhibitors. Here we use multiscale computational approach investigate thermodynamics apo enzyme and complex with two potent inhibitors, N3 ?-ketoamide 13b. We show that inhibitors free energy cost reach charge-separated sta...
