Daucosterol and Beta-Sitosterol – the Future-Ready phytochemicals from Terminalia chebula to combat SARS-CoV-2

The emergence of variants of SARS-CoV-2 over time raised the global concern that the strain might develop and modify again into new unknown variants in the future in an unprecedented manner, and the disease can be relapsed at any time, although it is declared as endemic. In this scenario, it becomes deemed necessary to identify, design, and formulate a future-ready drug that will be effective against the existing as well as new variants. In order to find out such types of drugs, we performed in silico screening of three phytochemicals, i.e.1,3,6-tri-O-galloyl-beta-D-glucose, Beta-Sitosterol and Daucosterol of Terminalia chebula , which were proved to be effective against SARS-CoV-2 Wild-type proteins in our previous report. In this study, we performed molecular docking experiments with those three phytochemicals against the fifteen variants of the spike protein of SARS-CoV-2 to find out the most effective candidate, which possesses the potential to inhibit the ACE2 receptor binding activities of the spike protein of the most of the variants. Our study showed that Beta-Sitosterol and Daucosterol exhibited the potential for strong binding to spike proteins of almost all variants through mainly hydrophobic interaction. Our results were further validated by MM-GBSA binding free energy calculations. This finding suggests that Beta-Sitosterol and Daucosterol can serve as potential drugs against most of the variants of SARS-CoV-2 and may be effective against the newly emerged variant. We believe that our finding, along with the validation by wet-lab experiments, can help the scientific and healthcare communities to prepare themselves against SARS-CoV-2 in the future.