Computational screening and biochemical analysis of and plants to find effective inhibitors against Receptor-Binding domain (RBD) of the spike protein of SARS-Cov-2.

Although World Health Organization-approved emergency vaccines are available in many countries, the mortality rate from COVID-19 remains high due to the fourth or fifth wave and the delta variant of the coronavirus. Thus, an effective mechanistic investigation in treating this disease is urgently needed. In this work, we extracted phytochemicals from two mangrove plants, and , assessing their potential actions against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. The antioxidant activities of leaves and fruits were 142.10 and 97.13 µg/mL, respectively, whereas leaves and fruits were 112.50 and 292.71 µg/mL, respectively. Furthermore, leaf extracts from both plants had lower cytotoxicity against than fruit extracts. Gas chromatography-mass spectrometry analysis revealed a total of 145 potential phytochemicals from these extracts. Three phytochemicals, 28-demethyl-beta-amyrone, 24-Noroleana-3,12-diene, and stigmasterol, displayed binding free energy values of - 8.3, -7.5, and - 8.1 Kcal/mol, respectively, in complexes with the spike protein of SARS-CoV-2. The root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, wet-lab validations are necessary to support these findings.