A benzimidazole scaffold as a promising inhibitor against SARS-CoV-2. Issue 5 (24th March 2023)

• Record Type: Journal Article
• Authors: Mudi, Prafullya Kumar; Mahanty, Ayan Kumar; Kotakonda, Muddukrishnaiah; Prasad, Sunnapu; Bhattacharyya, Subires; Biswas, Bhaskar
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 41:Issue 5(2023)
• Page Start: 1798
• Page End: 1810
• Publication Date: 2023-03-24
• Subjects: Benzimidazole -- crystal structure -- in vitro SARS-COV-2 screening activity -- MD simulations -- molecular docking -- green synthesis; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.2024448
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: The manuscript reports the green-chemical synthesis of a new diindole-substituted benzimidazole compound, B1 through a straightforward route in coupling between indolyl-3-carboxaldehyde and o-phenylenediamine in water medium under the aerobic condition at 75 ºC. The single crystal X-ray structural analysis of B1 suggests that the disubstituted benzimidazole compound crystallizes in a monoclinic system and the indole groups exist in a perpendicular fashion with respect to benzimidazole moiety. The SARS-CoV-2 screening activity has been studied against 1 × 10e4 VeroE6 cells in a dose-dependent manner following Hoechst 33342 and nucleocapsid staining activity with respect to remdesivir. The compound exhibits 92.4% cell viability for 30 h and 35.1% inhibition against VeroE6 cells at non-cytotoxic concentration. Molecular docking studies predict high binding propensities of B1 with the main protease (M pro ) and non-structural (nsp2 and nsp7-nsp8) proteins of SARS-CoV-2 through a number of non-covalent interactions. Molecular dynamics (MD) simulation analysis for 100 ns confirms the formation of stable conformations of B1-docked proteins with significant changes of binding energy, attributing the potential inhibition properties of the synthetic benzimidazole scaffold against SARS-CoV-2. Communicated by Ramaswamy H. Sarma