SARS-COV-2 Main Protease Inhibition by Bryophyllum Pinatum Phytochemicals: Computational and Kinetics Studies.

Background: The newly discovered coronavirus infection emerged in Wuhan, China in December 2019 and since then, there has been no FDA approved drugs used in the treatment of corona virus infection, presenting a major challenge to medicine. The protease enzyme in SARS-CoV-2 virus can be a target for the production drugs to manage COVID-19 because of its indispensable role in the replication of the virus. Results: A total of 102 phytochemicals were identified in Bryophyllum pinnatum any of which could be a potential inhibitor of 3CLpro. These 102 phytochemicals were screened by molecular docking for their binding energies, 3,6-diglucosylapigenin was chosen as lead compound after meeting all the ADMETox qualifications using quikprop software. 3,6-diglucosylapigenin with a binding energy of -10.59Kj/mol shows a good inhibitory activity similar to 3CLpro standard inhibitor; boceprevir. The amino acid interaction between the lead compound and the active site of the protease were examined. MD simulation was performed to analyse Root mean square fluctuation (RMSF), Solvent Accessibility surface area (SASA) and number of hydrogen bond and the results reveled a strong affinity between the 3CLpro and the lead compound. Furthermore, the binding energy of the lead compound was stronger than that of the standard inhibitor. Moreso, the RMSF was decreased at the active site of the enzyme as there was no fluctuation. However, far away from the active site, there was very high fluctuation, opening the active site of the enzyme leading to escape of the ligand. Conclusions: Ethanolic extract of Bryophyllum pinnatum was used for inhibiting the main protease of SARS-CoV-2 activity with the use of FRET assay to validate the study. Ethanol extracts from Bryophyllum pinnatum at 125.5µg/ml significantly inhibited 3CLpro activity at various concentrations of 100%, 50%, 30%, 10%, 3%, 0.3%, and 0.03%. This study identifies plant phytochemicals that can be a potential agent to combat COVID-19, and can eventually be used for future laboratory and clinical studies.