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.
Method: 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 electrostatic component of binding
free energies of 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-1
), there might be no big conformational change or loop reorganization, but involves only local conformational change typically observed in 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 SARS-CoV-2 entry and its subsequent infectivity. We postulate
that natural phytochemicals like Tinocordiside could be the viable options for controlling SARS-CoV-2 contagion and its
entry into host cells.