Background::
COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive
analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing
the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of
SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered
as potential drug target to combat the current pandemic.
Methods::
Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2
by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir.
The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore,
average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like
abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed
to predict the strength of interaction.
Results::
Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident
from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3
Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable
conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were
computed which was observed to be concordant with results of molecular docking study. RMSD average values were found
to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and
fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied
cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor
interaction. ADMET exploration further validated the drug like properties of these compounds.
Conclusion::
Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially
used to target SARS-CoV-2 by hindering its replication process.
Torsional Energy Barriers of Biaryls Could Be Predicted by Electron Richness/Deficiency of Aromatic Rings; Advancement of Molecular Mechanics toward Atom-Type Independence