All the molecular dynamics simulations were performed using standard dynamics cascade protocol of BIOVIA Discovery studio. The top docked poses of all the M Proinhibitor complexes were further edited by protonating at pH 7.4 at dielectric constant of 10 and subjected to CHARMM36 force field. Each system was placed in the centre of the orthorhombic simulation box modeled by the explicit periodic boundary solvation model. A minimum distance from the edge of the box was set to 7 Å and 0.145 (M) NaCl was added to each of the systems. The protein only (M Pro ), protein-reference complex (M Pro -famotdine), and three final protein-inhibitor complexes (M Pro -CNP0416047, M Pro -3-hydroxyanisotine, M Pro -anisotine) were solvated with 6358, 6335, 6332, 6313, 6325 no of water molecules in the orthorhombic simulation box. All the solvated systems were minimized in two stages to sort out poor contacts within the system and to warrant the systems to gain a low energy point as required for the successive stages. Then the solvated systems were subjected to 2000 steps of the steepest descent algorithm in the first step followed by the 5000 steps of the conjugate gradient. Additionally, each of the minimized systems was slowly heated from 50 K to 300 K at a time period of 120 ns. Then the systems were equilibrated for 1 ns at a constant temperature of 300 K. In both the heating and equilibration steps, the adjusted velocity frequency was set to 50. The production step was performed for 20 ns for each of the systems using NVT ensemble at 300 K. The results of the production steps were saved after every 2 ps. During the simulation, the non-bond higher cut-off distance and lower cut-off distance were kept at 12 Å and 10 Å respectively, and the spherical cut-off method was used for the electrostatics calculation.