Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS--
CoV-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.