Using Avogadro 1.2 software, ligand structures were drawn and optimized by the universal force field (UFF) . Further optimization was performed utilizing the parameterization method 6 (PM6) of SCIGRESS 3.0 software followed by infra-red calculations at the same level of the semi-empirical method . The positive control ligands O6K and N3 were also optimized using the same protocol after retrieval from the PDB structures 6Y2G and 6LU7, respectively . Finally, all the ligands were prepared for docking by AutoDock tools 1.5.6 software . Charges (Kollman and Gasteiger) were added while the PDBQT files of the ligands were saved for the docking calculations. Meanwhile, the M pro structure (PDB ID: 6Y2G) was separately prepared for the MD simulations and the MDock studies.