Benzimidazole Derivatives as Potential Inhibitors of Monkeypox A41 Protein: DFT Calculations, Molecular Docking, ADME, and Toxicity Assessments

Abstract

Abstract The emergence of monkeypox virus (Mpox) infection poses a significant and worrying danger to the human world. The absence of pharmaceutical compounds to treat the disease might make the problems worse. Identifying prospective pharmacological targets may greatly enhance the process of generating highly effective chemical molecules for the treatment of the Mpox virus. In this study, five new benzimidazole derivatives ( 1a‐e ) were synthesized and characterized using FT‐IR and 1 H‐NMR. Quantum chemical calculations at the density functional theory (DFT) level were performed on compounds ( 1a‐e ) and on Tecovirimat ( 2 ), used as a reference molecule, to compute the most stable molecular conformation and its electrostatic and electronic properties. Molecular docking studies revealed that the effectiveness of compounds ( 1a‐e ) is comparable to that of Tecovirimat ( 2 ), an FDA‐approved antiviral molecule against the Mpox virus, responsible for many side effects. The interaction of 1c compound with protein 8JC6 causes the most negative binding energy (−6.017 kcal/mol), while the calculated value for 2 compound is −5.442 kcal/mol. Other compounds ( 1a , 1b , 1d , and 1e ) show a good binding energy for 8JC6 (−5.206, −5.825, −5.682, and −5.855 kcal/mol, respectively). Pharmacokinetics and toxicity analysis also revealed good antiviral candidacy of these compounds, which may therefore be recommended as new antiviral agents to combat the Mpox virus.