Fig. 1. (A) Computational scheme was applied to characterize and design potential inhibitors for SARS-CoV-2 Mpro using atomistic simulations and machine learning calculations. (B) A ligand was docked to SARS-CoV-2 Mpro using AutoDock Vina. (C) The protonation states of the catalytic dyad His41 and Cys145. (D) A ligand was dissociated from the bound state using external-harmonic force during FPL simulations. was put on the ligand center of mass in order to force the ligand to mobilize out of the protease binding cavity.