Imidazoles and benzimidazoles as putative inhibitors of SARS-CoV-2 B.1.1.7 (Alpha) and P.1 (Gamma) variant spike glycoproteins: A computational approach.

COVID-19 is an unprecedented pandemic threatening global health, and variants were discovered rapidly after the pandemic. The two variants, namely the SARS-CoV-2 B.1.1.7 (Alpha) and P.1 (Gamma), were formed by the mutations in the receptor binding domain of spike glycoprotein (SGP). These two variants are known to possess a high binding affinity with the angiotensin-converting enzyme 2. Amidst the rapid spread of these mutant strains, research and development of novel molecules become tedious and labour-intensive. Imidazole and benzimidazole scaffolds were selected in this study based on their unique structural features and electron-rich environment, resulting in increased affinity against a variety of therapeutic targets. In the current study, imidazole- and benzimidazole-based anti-parasitic drugs are repurposed against SARS-CoV-2 Alpha and Gamma variant spike glycoproteins using computational strategies. Out of the screened 15 molecules, flubendazole and mebendazole have exhibited promising binding features to the two receptors (PDB ID: 7NEH and 7NXC), as evidenced by their glide score and binding free energy. The results are compared with that of the two standard drugs, remdesivir and hydroxychloroquine. Flubendazole and mebendazole have become convenient treatment options against mutant lineages of SARS-CoV-2. The edge of the flubendazole was further established by its stability in MD simulation conducted for 100 ns employing GROMACS software. Further, in vitro and in vivo studies are essential to understand, if flubendazole and mebendazole indeed hold the promise to manage SARS-CoV-2 mutant stains. GRAPHIC ABSTRACT: SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01900-8.