LAUSR

BACKGROUND 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. METHOD 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 both the binding affinity and interacting 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 a 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.