Novel Cephalosporins Against the Main Protease of SARS CoV (Mpro O, Mpro WT): Molecular Docking and DFT Study

Abstract

Our study predicts potential inhibitors targeting nucleophilic catalytic dyed residues H41 and C145 of M^pro _WT and M^pro omicron (M^pro O) following drug designing method protocols. Docking studies were used to find potent and efficient inhibitors that can compete with ATP for binding to a particular target protein location. Both proteins' structures were docked against library of cephalosporin derivatives, that is, M^pro _WT and M^pro omicron are predicted with binding energy (ΔG bind-PB) in range −11.501 to −14.8396 kcal/mol. It has been discovered that several kinds of residues, particularly His41, Cys145, Gly143, Gln189, His132, and Gln109, are necessary for the continual existence of inhibitors in the active pocket. DFT studies were also carried out to calculate optimized geometries, energies of HOMO–LUMO, MEP, and global chemical reactivity descriptors were obtained. In addition, the ¹H-NMR chemical shift of compounds was calculated using the GIAO method; the shifts of the molecules are in good agreement with the experimental value. In this series, compound 3N has the lowest ∆E value (3.31 eV) and compound 3C has the highest ∆E value (3.66 eV) showing them the most and the least reactive, respectively. According to this research, these ligands appear to have a bright future as SARS-CoV-2 treatment drugs.