The high-resolution X-ray crystal structure of the protein (M Pro ) was retrieved from RCSB PDB bank (PDB ID: 6LU7) and crystal structure was analyzed as required for the measurement of cavity size/distances/charge/shape for the structure-based drug discovery. The PyMol molecular visualization system and BIOVIA Discovery Studio Client were utilized for protein structure visualization, structure alignment and for the measurement of the distance between residues and the diameter of cavity size. The protein structure was further edited and refined as required for the docking and simulation protocol as mentioned in the specific sections. The structure of the ligand molecules was obtained from COCONUT (Collection of natural product database) and NPBS (Natural product and biological source) . At first, the structures were drawn in ChemDraw ultra 12.0 and then Geometry optimization of the alkaloid molecules was carried out using DFT at the B3LYP (1,2) /6-31+G(d,p) level of theory in Gaussian suite of program . The geometry optimized ligand structures were subjected to refinement as required for docking as mentioned in the specific sections.