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