The initially selected nine alkaloids from the screening were further subjected to the advanced flexible docking against SARS_CoV_2 M Pro along with the reference famotidine to assess the structure based interactions. Purposefully, the CDOCKER program of BIOVIA Discovery studio (25) equipped with flexible docking at variable temperatures using CHARMm based energy function was utilized for the detailed structure-based assessment of binding. As these alkaloids were found to be catalytic cavity binders in rigid docking as shown in screening section, therefore the flexible dockings were carried out inside the active site cavity sphere encompassing all subsites and crucial residues. The alkaloids were docked separately using customized protocol as described in materials and method section, and were ranked according to their best negative CDOCKER Interaction energies as shown in Table .