MD simulation of the M pro structure was performed by the NAMD 2.13 software utilizing CHARMM 36 force field . The calculations were performed for 100 ns over the SHAHEEN HPC platform in the King Abdullah University for Science and Technology (KAUST), Saudi Arabia (project no. 1482). The simulation was performed in the TIP3P water model at 1 atm, and 310 K with NaCl added for the protein-water solution to be of a total concentration of 154 mM . Periodic boundary condition was utilized with a cubic simulation box. After the simulation, the trajectories were clustered using UCSF Chimera software 1.14 and analyzed, as will be shown in the results section using VMD 1.9.3 software and in-house codes . After the binding energy calculations, we ranked the ligands according to their binding energies to (M pro ). The best two ligand-M pro complexes (8-M pro and 9-M pro ) and the O6K-M pro complex were subjected to another 100 ns MD simulations run with the same protocol. After the run, the Molecular Mechanics-Generalized Born Oppenheimer Surface Area (MM-GBSA) was calculated using Amber tools to deconvolute the binding affinity as a per-residue contribution .