Abstract
Background: The establishment of strategy to inhibit the virus replication is
an attractive means in combating SARS-CoV-2 infection.
Objective: We studied phyto-compounds from Strychnos nux-vomica (a poisonous
plant) against SARS-CoV-2 RNA-dependent RNA polymerase by computational
methods.
Methods: Molecular docking, molecular dynamics (MD) simulation and energetics
calculations were employed to elucidate the role of the phyto-compounds.
Results: Ergotamine with a binding free energy of -14.39 kcal/mol showed a promising
capability in terms of binding affinity and the interaction to conserved motifs, especially
the SDD signature sequence. The calculated dissociation constants for ATP,
ergotamine, isosungucine and sungucine were 12 μM, 0.072 nM, 0.011 nM and 0.152
nM, respectively. The exhibited kd by these phyto-compounds reflected tens of
thousands fold potency as compared to ATP. The binding free energies of sungucine
and isosungucine were much lower (-13.93 and -15.55 kcal/mol, respectively) compared
to that of ATP (-6.98 kcal/mol).
Conclusion: Sharing the same binding location as that of ATP and having high binding
affinities, Ergotamine, Isosungucine, Sungucine and Strychnine N-oxide could be
effective in controlling the SARS-CoV-2 virus replication by blocking the ATP and
inhibiting the enzyme function.
Keywords:
SARS-CoV-2, RNA-dependent RNA polymerase, inhibition, Strychnos nux-vomica, phyto-compounds, computational methods
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and
Anurag Varshney*
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