4. DISCUSSION:
Mushrooms are found to possess antiviral activity also they are reviewed
to have therapeutic effect against inflammation and pneumonic
superinfection against recent global pandemic of COVID-1929. We focused on the edible mushrooms which are
commonly available in the markets rather than deep search in the forest
and examined the main compounds which has broad activity against upper
respiratory viruses via literature review and found out four compounds
fall into the above categories mentioned. And targets Main Protease
(Mpro) and Spike Protein were chosen to see the inhibitory effect of the
ligands on the pre-entry stage and protein cleavage stage in the life
cycle of the SARS-CoV-2 virus leading to disruption and decrease of the
viral load in vivo . And also due to recent outbreak of different
variants, whose mutation took place in the spike protein of the
SARS-CoV-2 virus, thankfully they carry similar inhibition sites and the
most mutation took place in the furin loops and so the spike protein was
chosen as the target of interest 30.
The ligands were successfully docked against inhibition site of Main
Protease with following docking scores -1.068 Kcal/ mol for Eritadenine,
-3.617 Kcal/ mol for Gallic Acid, -0.420 Kcal/ mol for Ergosterol
Peroxide and -5.035 Kcal/ mol for Pleuran respectively. Similarly, the
ligands also docked successfully against Spike Protein with docking
scores such as -0.783 Kcal/ mol for Eritadenine, -2.140 Kcal/ mol for
Gallic Acid, 1.027 Kcal/ mol for Ergosterol Peroxide and -5.241 Kcal/
mol for Pleuran respectively. And the docked complexes exhibited
convergence within 10 ns of molecular dynamics whose RMSD values ranged
from 1Å to 2.5Å for all ligands which has been bound to Main protease
and RMSF values ranged from 5Å to 6.5Å. Similarly, RMSD values ranged
from 1Å to 2Å and also the RMSF values ranged from 0.5Å to 3.5Å
respectively in the Spike Protein target, therefore all protein ligand
complexes are stable in both targets according to results in RMSD
analysis as well as in RMSF analysis. All complexes expressed strong
hydrogen bonding throughout the time of molecular dynamics simulation
through which it gives an inference that the protein ligand complexes
are stable 31. All other compounds except pleuran did
express good druggability properties during in silico ADME
analysis. Similarly, during target analysis the compounds except pleuran
showed good targeting against protease enzymes. But in literature
pleuran has been found to express good activity against protease enzymes
and also effective in progressivity towards being a drug and also has
immunomodulatory effect 32. Based on toxicity all
ligands expressed minimum toxicity levels except eritadenine but are
mostly non-toxic to the important organs such as liver, heart and
kidneys based on the simulation projected in the results.
When comparing these compounds with already repurposed drugs such as
Lopinavir , Famciclovir, Drunavir, Amprenavir and N3 whose docking
scores are -9.918 Kcal/ mol, -7.546 Kcal/ mol, -7.505 Kcal/ mol, -8.655
Kcal/ mol, -7.5 Kcal/ mol respectively. And the repurposed drugs which
are mentioned above exhibit higher docking score than the compounds of
interest 33, 34. The ligand of interest has lesser
docking score and has more significance. Therefore the compounds which
were studied can be used for therapeutic purposes against COVID-19. We
the authors also propose as the inhibition site of all spike proteins in
variants of concern are similar, one particular drug or a compound which
has been studied to have inhibitory effect can be used to treat
SARS-CoV-2.