Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

Abstract

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is 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 was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. 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. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

Natural and Synthetic Drugs as Potential Treatment for Coronavirus Disease 2019 (COVID-2019)

“…Patel and his coworkers have explored the fungal metabolites i.e. quercitrin (G. triplex), bergenin (D. indusiata) and dihydroartemisinin (C. stercoreus) through computational studies, which shows potential remedies to inhibit the main protease of SARS-CoV-2 [126].…”

Liquiritin from Glycirrhyza Glabra L (Fabaceae) - a Natural Derived Drug, as a Potential Inhibitor for SARS-CoV-2

“…Nature has always overwhelmed us with many new and unique bioactive compounds which possess potential activity against various disease and infection (8). Hence, there is prerequisite of scientific community to draw the diverse knowledge of traditional system (9).…”