2.1.  Preparation of protein and ligand structures
The spike protein and main protease regulatory enzyme of SARS-CoV-2 have been revealed to play a vital role in COVID-19 infection in the host (Ke et al., 2020; Xue et al., 2008). In order to delineate the drug treatment, the deduced three dimensional structures of target SAR-CoV-2 spike protein in open state (PDB ID: 6VYB) and main protease (PDB ID: 6LU7) were retrieved from RCSB Protein Data Bank (Burley et al., 2019). The crystal structures of target proteins were imported to Schrödinger Maestro (Moore, 2015) for molecular docking analysis. Pre-processing and preparation of target proteins were performed using Schrödinger Protein Preparation Wizard (Schrödinger, 2011) by adding the missing hydrogen atoms, correcting the bond orders, capping the protein termini, creating disulfide bonds and removing the water molecules. Also, the H-bonds were optimized and further the target proteins were equilibrated using OPLS 2005 force field (Robertson et al., 2015).
The library of ligands was downloaded from DrugBank (Wishart et al., 2018) and the coordinate files were prepared and optimized using LigPrep module (Release, 2017). The energy minimization of ligand structures was carried using OPLS 2005 force field and ionization states were generated at pH 7.0 ± 2.0 using Epik. This generated an output file with various stereoisomers and tautomeric conformers of each ligand producing chemical and structural diversity.