Investigation of ZINC85862539_679 to inhibit SARS-CoV-2 main protease: DFT calculation and molecular docking

In this study, the molecular geometry structure of ZINC85862539_679 compound was performed by density functional theory (DFT) calculation at B3LYP level 6-311++G(d,p) basis set. The energies gap of HOMO-LUMO (highest occupied molecular orbital, HOMO and lowest unoccupied molecular orbital, LUMO) of ZINC85862539_679, and chemical reactivity descriptors were also investigated. The molecular electrostatic potential (MEP) has also been carried out using the DFT method. Additionally, the inhibition of ZINC85862539_679 on the main protease (M-pro) of SARS-CoV-2 was investigated using molecular docking approach. Our results indicated that nine hydrogen bonds (Cys145, Thr26, Thr25, Thr45, Thr24, Ser46, Tyr54, Arg188, Met165) and one Pi-Alkyl interaction at Leu27, and one Pi-Sulfur interaction at Cys145 between this compound with SARS-CoV-2 M-pro. The docking score of ZINC85862539_679 (-14.3 kcal/mol) is better than the one of remdesivir (-8.1 kcal/mol). Therefore, ZINC85862539_679 can be considered as a potential inhibitor of SARS-CoV-2 M-pro, which needs to be explored further for future drug development.