Flexible docking between SARS_CoV_2 M Pro with screened alkaloids and reference compound famotidine were performed using CDOCKER program of BIOVIA Discovery studio for detailed structure-based assessment of binding. The retrieved protein structure from RCSB database was initially subjected to 'clean protein' protocol to eradicate alternate conformations, and any error in bond order and amino acid sequence. Thereafter, the protein was further subjected to protonation at pH 7.4 and ionic strength 0.145 (M) respectively. In addition, the CHARMm force field was applied in vacuo for the global energy minimization of the protein structure. For the targeted docking to the active site of the protein, site sphere was created with co-ordinates set to -12.0702, 13.4652, and 68.368 respectively. Finally, the CDOCKER program was executed with customized parameters where the pose cluster radius was set to 0.5, total random conformations were set to 10, total dynamics steps were set to 1000. Additionally, in the simulated annealing section heating steps and target temperature were set to 2000 and 700 K simultaneously, cooling steps and target temperature was 5000 and 300 K simultaneously. After each docking, ten docking conformers were ranked automatically based on -CDOCKER energy, and evaluated further for molecular-level analysis of the bindings.