2.1. Preparation of dataset

The protein structure used in our study was obtained from the Protein Data Bank (PDB ID: 6LU7) and was prepared using Schrödinger's protein preparation wizard. 21 Hydrogen bond optimizations, water removal, protein structure correction, and finally protein energy minimization using OPLS_2005 force field were carried out during the preparation. Subsequently, the position of N3 (cocrystallized native ligand; used as the reference compound) was defined for grid generation. Further, a set of nine molecules consisting of the substructure of the cocrystallized ligand of SARS‐CoV‐2 protease, a cocrystallized ligand, three substructures of equivalent SARS‐CoV‐1 protease inhibitors, and four known SARS‐CoV‐1 inhibitors with low binding affinity were extracted from the literature. 22 These molecules were then cleaned using default specifications of the LigPrep module and utilized for hypothesis generation. 21 Additionally, a phase database was generated from a total of 9591 molecules retrieved from DrugBank and was utilized for virtual screening application. 23