Tinocordiside from Tinospora cordifolia (Giloy) May Curb SARS-CoV-2 Contagion by Disrupting the Electrostatic Interactions between Host ACE2 and Viral S-Protein Receptor Binding Domain
| Autor: | Subarna Pokhrel, Anurag Varshney, Acharya Balkrishna |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Conformational change biology Chemistry Organic Chemistry General Medicine Tinospora cordifolia Ligand (biochemistry) Entry into host biology.organism_classification Computer Science Applications 03 medical and health sciences Molecular dynamics 0302 clinical medicine Docking (molecular) 030220 oncology & carcinogenesis Drug Discovery Biophysics Receptor 030304 developmental biology Binding domain |
| Zdroj: | Combinatorial Chemistry & High Throughput Screening. 24:1795-1802 |
| ISSN: | 1386-2073 |
| DOI: | 10.2174/1386207323666201110152615 |
| Popis: | Background: SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells. Objective: We have screened phytocompounds from a medicinal herb, Tinospora cordifolia, for their capacities to interrupt the viral RBD and host ACE2 interactions. Methods: We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy. Results: ‘Tinocordiside’ docked very well at the center of the interface of ACE2-RBD complex, and was found to be well stabilized during MD simulation. Tinocordiside incorporation significantly decreased the electrostatic component of binding free energies of the ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). As the basal rate constant of protein association is in the order of 5 (105 to 106 M-1S-1), there might be no big conformational change or loop reorganization, but involves only local conformational change typically observed in the diffusion-controlled association. Taken together, the increase in global flexibility of the complex clearly indicates the start of unbinding process of the complex. Conclusion: It indicates that such an interruption of electrostatic interactions between the RBD and ACE2, and the increase in global flexibility of the complex would weaken or block SARSCoV- 2 entry and its subsequent infectivity. We postulate that natural phytochemicals like Tinocordiside could be viable options for controlling SARS-CoV-2 contagion and its entry into host cells. |
| Databáze: | OpenAIRE |
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