Additionally, we calculated the radius of gyration (Rg) to measure the changes in compactness of protein molecule after the binding of inhibitors. As Rg value determines the packing of the three dimensional structure of protein molecule, therefore generally a favorable binding of ligand lowers down the Rg value. As we measured the Rg values for 20 ns simulation run of unligated M Pro and M Proinhibitor complexes, it was observed that Rg for unligated M Pro was 2.274 ± 0.013 nm, whether Rg for M Pro -famotidine, M Pro -CNP0416047, M Pro -3-hydroxy anisotine, M Pro -anisotine were 2.266 ± 0.012 nm, 2.274 ± 0.011 nm, 2.269 ± 0.012 nm, and 2.263±0.013 nm respectively (Table , Supplementary Figure ). Therefore, the calculated Rg values signify that the unligated protein became more compact in nature due to complexation with the inhibitor molecules and gained stabilities.