3.5.1. Protein and Ligand Preparation

The 3CL hydrolase (Mpro) of SARS-CoV-2 had been exploited as a potential drug target to fight COVID-19 [27]. Thus, the virtual screening was conducted by using the SARS-CoV-2 enzyme (PDB ID 6LU7) obtained from the Protein Data Bank (PDB, http://www.rcsb.org/pdb), and the structure was optimized by using the protein preparation wizard module in Maestro software package (Schrodinger LLC, NY, USA). Specifically, the water and heteroatom were removed, the polar hydrogens were added to the protein to the protonation state, the entire structure was assumed as a neutral pH, and the energy of the structure was minimized by using an OPLS2005 force field. The docking grid of 20 Å size was generated over the co-crystallized ligand. All compounds 1–17 were implemented by Ligprep software, and the structure energy was minimized using OPL2005 force field.
