Computational Exploration of Mutant SARS-CoV-2 Main Protease as a Target for Binding and Inhibition Attributes Utilizing Antiviral Drugs for Therapeutic Application

The main protease (Mpro) of SARS-CoV-2 signifies a significant focus for antiviral drug development, serving as a vital enzyme in the virus's life cycle. The inhibition of SARS-CoV-2 Mpro constitutes a promising approach for developing therapeutic agents intended for the treatment of SARS-CoV-2 and similar viruses. This study investigates the structural, functional, binding, and inhibition attributes of the SARS-CoV-2 Mpro by implementing protein flexibility modeling and docking with selected antiviral agents, including Acyclovir, Remdesivir, Sofosbuvir, Atazanavir, Cidofovir, Indinavir, Lopinavir, Oseltamivir, Galidesivir, and Favipiravir. Protein flexibility modeling revealed that the maximum fluctuation occurred at residue index 306, with an average RMSF value of 3.8 Å. The lowest binding affinity observed for the Mpro-Atazanavir complex was determined to be -8.1 Kcal/mol, corresponding to a Ki value of 5.95 µM. The docked lowest binding affinity was found for the common active site residues, including GLN-110, ASN-151, VAL-202, HIS-246, ILE-249, PRO-252, PHE-294, and VAL-297, which involve hydrogen bond interactions between the protein and ligands. Selected antiviral drugs exhibit adequate binding affinity and inhibitory effectiveness; hence, comparable chemical property compounds may be selected to repurpose viable therapeutic candidates as Mpro inhibitors.