Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of
Severe Acute Respiratory Syndrome (SARS) and
Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-
PBSA studies of fifteen bioactive
bioflavonoids derived from plants as a plausible potential
antiviral in the treatment of
COVID-19. Molecular docking studies for 15
flavonoids on the three SARS CoV-2
proteins, non-structural protein-15
Endoribonuclease (NSP15), the receptor-binding domain of spike
protein (RBD of S
protein), and main
protease (Mpro/3CLpro) were performed and selected
protein-
ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-
PBSA method. All
flavonoids were further assessed for their effectiveness as adjuvant
therapy by network pharmacology analysis on the target
proteins. The network pharmacology analysis suggests the involvement of selected
bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF,
adipocytokine, and leukocyte transendothelial migration which plays a significant role in
immunomodulation, minimizing the oxidative stress and
inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of
glycyrrhizic acid,
amentoflavone, and mulberroside in inhibiting key SARS-CoV-2
proteins and these results could be exploited further in designing future
ligands from natural sources.