Molybdenum Carbonyl Complexes with Benzimidazole Derivatives Against SARS-CoV-2 by Molecular Docking and DFT/TDDFT Methods

Abstract

Benzimidazole derivative molecules attract attention of scientists due to their bioactivities. The dramatic changes in recorded activities according to the type and position of the substituents motivate synthesis and analysis of new molecules. Commercial benzimidazole-based molecules have been used in therapeutic procedures. It is known that the activities of metal complexes with benzimidazole derivative ligands have different activities when compared to the benzimidazole main structure. Nowadays, one of the most important health problems is COVID-19, which caused the pandemic that we are still experiencing. Although vaccine studies are important to overcome acute problems, regarding the possible post-vaccination adverse effects, the need for new drugs against the virus is obvious. Considering the urgency and the limited facilities during the pandemic, preliminary in silico studies of candidate molecules are essential. In this study, {[bis-(N-benzylbenzimidazole)] tetracarbonylmolybdenum}, {[bis-(N-4-chlorobenzylbenzimidazole)] tetracarbonylmolybdenum} and {[bis-(N-4-methoxybenzylbenzimidazole)] tetracarbonylmolybdenum} were synthesized and characterized. The optimization and the structural analysis of these molecules were performed by DFT/TDDFT methods. The molecules were docked into SARS coronavirus main peptidase (PDB ID: 2gtb), COVID-19 main protease in complex with Z219104216 (PDB ID: 5r82), COVID-19 main protease in complex with an inhibitor N3 (PDB ID: 6lu7) and Papain-like protease of SARS-CoV-2 (PDB ID: 6w9c) crystal structures for evaluation of their anti-viral activity.

Metallo-antiviral aspirants: Answer to the upcoming virus outbreak

“…Three complexes Mo-1 to Mo-3 ( Fig. 4 ), were synthesized, characterized, and investigated against peptidase, 3CLpro, and PLpro protein targets of SARS coronavirus, under docking mode [ 65 ]. The binding free energy ( ΔG ) of these molecules with different target proteins was calculated and obtained in the range between −7.86 and −5.09 kcal/mol for Mo-1 , -8.48 to −6.18 kcal/molfor Mo-2 , and -8.43 to −5.29 kcal/molfor Mo-3 .…”