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
; 24(10): 1795-1802, 2021.
Article
in English
| MEDLINE | ID: covidwho-918979
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Tinospora
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
Glycosides
Type of study:
Experimental Studies
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
Comb Chem High Throughput Screen
Journal subject:
Molecular Biology
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
1386207323666201110152615
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