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

Abstract

AbstractIn 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 (Mpro) 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 Mpro. 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 Mpro, which needs to be explored further for future drug development.