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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.
Comb Chem High Throughput Screen. 2021; 24(10):1795-1802.CC

Abstract

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.

Authors+Show Affiliations

Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand, India.Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand, India.Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33172372

Citation

Balkrishna, Acharya, et al. "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." Combinatorial Chemistry & High Throughput Screening, vol. 24, no. 10, 2021, pp. 1795-1802.
Balkrishna A, Pokhrel S, Varshney A. 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. Comb Chem High Throughput Screen. 2021;24(10):1795-1802.
Balkrishna, A., Pokhrel, S., & Varshney, A. (2021). 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. Combinatorial Chemistry & High Throughput Screening, 24(10), 1795-1802. https://doi.org/10.2174/1386207323666201110152615
Balkrishna A, Pokhrel S, Varshney A. 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. Comb Chem High Throughput Screen. 2021;24(10):1795-1802. PubMed PMID: 33172372.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Balkrishna,Acharya, AU - Pokhrel,Subarna, AU - Varshney,Anurag, PY - 2020/07/07/received PY - 2020/09/30/revised PY - 2020/10/11/accepted PY - 2020/11/12/pubmed PY - 2021/10/1/medline PY - 2020/11/11/entrez KW - ACE2-RBD complex KW - COVID-19 KW - SARS-CoV-2 KW - Tinospora cordifolia KW - docking KW - electrostatic component of binding free energy. KW - molecular dynamics simulation KW - tinocordiside SP - 1795 EP - 1802 JF - Combinatorial chemistry & high throughput screening JO - Comb Chem High Throughput Screen VL - 24 IS - 10 N2 - 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. SN - 1875-5402 UR - https://www.unboundmedicine.com/medline/citation/33172372/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_ L2 - https://www.eurekaselect.com/187793/article DB - PRIME DP - Unbound Medicine ER -