In-silico Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors against Main Protease of SARSCoV- 2

Abstract

Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Methods: High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum triplex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and dihydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Results: A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion: Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.