Phyto-Compounds from a Rather Poisonous Plant, Strychnos nuxvomica, Show High Potency Against SARS-CoV-2 RNA-Dependent RNA Polymerase
| Autor: | Acharya Balkrishna, Anurag Varshney, Subarna Pokhrel |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
biology
SARS-CoV-2 Chemistry Stereochemistry COVID-19 Strychnos nux-vomica RNA-dependent RNA polymerase Strychnos General Medicine Strychnine biology.organism_classification Biochemistry Molecular Docking Simulation Dissociation constant Ergotamines Plants Toxic chemistry.chemical_compound Adenosine Triphosphate Viral replication RNA polymerase RNA Viral Molecular Medicine Potency Molecular Biology |
| Zdroj: | Current Molecular Medicine. 22:929-940 |
| ISSN: | 1566-5240 |
| DOI: | 10.2174/1566524021666210218113409 |
| Popis: | 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. 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 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. |
| Databáze: | OpenAIRE |
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