The hit alkaloids CNP0416047, 3-hydroxy anisotine, and anisotine were subjected to molecular dynamics simulation along with reference famotidine to examine the conformational stability and compactness of the their complexes with the target. Purposefully, the unligated protein (only M Pro ) and protein-hit complexes (M Pro -famotidine, M Pro -CNP0416047, M Pro -3-hydroxy anisotine, and M Pro -anisotine) were simulated for 20 ns using BIOVIA Discovery Studio-Standard Dynamics Cascade program using the customized protocol as mentioned in materials and method section. In each simulation run, trajectories of 10,000 conformations were analyzed and several properties like RMSD, RMSF, radius of gyration, and binding energy were explored.