anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles.

The manuscript deals with cost-effective synthesis, structural characterization and SARS-CoV-2 screening activity of 5-membered heterocycle-substituted benzimidazole derivatives, 1-((1H-pyrrol-2-yl)methyl)-2-(1H-pyrrol-2-yl)-1H-benzo[d]imidazole (), 2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzo[d]imidazole (), 2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole (). The benzimidazole compounds were synthesized through a green-synthetic approach by coupling of 5-membered heterocyclic-carboxaldehyde and o-phenylenediamine in water under an aerobic condition. The compounds were characterized by various spectroscopic methods and X-ray structural analysis. The suitable single-crystals of the methyl derivative of were grown as which crystallized in a monoclinic system and the thiophene groups co-existed in a nearly a perpendicular orientation. Further, anti-SARS-CoV-2 proficiency of the synthetic derivatives is evaluated against main protease (M) and non-structural proteins (nsp2 and nsp7) of SARS-CoV-2. Molecular docking and molecular dynamics analysis of the ligands () against M and nsp2 and nsp7 for 50 ns reveal that turns out to be the superlative antiviral candidate against M, nsp2 and nsp7 of SARS-CoV-2 as evident from the binding score and stability of the ligand-docked complexes with considerable binding energy changes.