The binding affinity of rutin against both spike and main protease were investigated through MD simulations using GROMACS. Separate MD simulations for spike protein and main protease with and without rutin for 100 ns were assessed through trajectory analysis. For the course of 100 ns MD simulation, the stable trajectory was observed and the representative structures were obtained. The deviation of the backbone atoms for simulated structures relative to the starting structures used as a reference was evaluated through RMSD for the backbone atoms (Figures 2 and 3) and C-alpha atoms (supporting material Figure S1). A steep magnitude RMSD variation during the entire simulation can be an implication of a malleable and free instinctive protein or the alteration of the force field. Depending upon the outcomes of the RMSD evaluation, Figure 2(A) represents that the RMSD fluctuation stabilize at about 50 ns MD simulations for both spike protein and spike protein in presence of rutin, and the simulation time was acceptable. In the time from 50–100 ns, the RMSD for spike protein and spike-rutin complex have approximate values about 1.50–1.65 nm and 1.20–1.26 nm, respectively. Similarly, the main protease in absence and presence of rutin for time from 20–70 ns and 20–100 ns showed RMSD values of about 0.25–0.30 nm and 0.20–0.25 nm (Figure 3(A)). Interestingly, RMSD for both the complex systems were more stable than the native state of target receptor spike protein and main protease (Figures 2(A) and 3(A)). The RMSD of C-alpha atoms were also attained and was found to be similar to the RMSD of backbone atoms (supporting material Figure S1). The average RMSD for backbone and C-alpha atoms of both the protein and their complex with rutin are shown in supporting material Table S1.