*6.5.2.1 Retrieval and preparation of ligands and receptor*

A small molecule–protein molecular docking study is based on the prediction of probable interactions between the ligand and its receptor. Obtaining the threedimensional structures of both the ligand and receptor is the first vital step for performing a molecular docking process. Therefore, the raw three structures of a set of FDA-approved antiviral protease inhibitors, as well as 3CLpro from *SARS-CoV-2*, were retrieved from the drug bank database (https://go.drugbank.com/) and protein data bank (https://go.drugbank.com/) respectively. The subjected drugs (**Table 4**) were obtained in the sdf format, and their raw structures were further prepared by adding polar hydrogens, computing Gastieger charge, detecting the root atom, setting the torsion, and the number of torsions. Furthermore, the structure of the 3CLpro was also optimized by deleting water molecules and bound ligands, adding polar hydrogens and Kollman charge using the Python molecule viewer software.
