马钱子的植物化合物显示出对SARS-CoV-2 RNA依赖的RNA聚合酶的高效力

Title:Phyto-Compounds from a Rather Poisonous Plant, Strychnos nuxvomica, Show High Potency Against SARS-CoV-2 RNA-Dependent RNA Polymerase

Volume: 22 Issue: 10

关键词: SARS-CoV-2, RNA依赖RNA聚合酶，抑制，马钱子，植物化合物，计算方法

摘要:

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.

Cite this article as:

Phyto-Compounds from a Rather Poisonous Plant, Strychnos nuxvomica, Show High Potency Against SARS-CoV-2 RNA-Dependent RNA Polymerase, Current Molecular Medicine 2022; 22 (10) . https://dx.doi.org/10.2174/1566524021666210218113409