A benzimidazole scaffold as a promising inhibitor against SARS-CoV-2

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

Keywords:

• Benzimidazole
• crystal structure
• in vitro SARS-COV-2 screening activity
• MD simulations
• molecular docking
• green synthesis

Acknowledgement

The authors sincerely thank to the Advanced Technology Platform Centre, Regional Centre for Biotechnology, Faridabad, India for carrying out the in vitro antiviral studies of two synthetic compounds (phenazine and B1) against VeroE6 cell on payment basis. The authors sincerely acknowledge the Centre for Biotechnology and Phyto Pharmacognosy Research, Coimbatore, India to support the measurement of biological activities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Dr. Bhaskar Biswas gratefully acknowledge the financial support received from the University of North Bengal, Darjeeling 734013.