The SARS-CoV-2 spike protein and main protease were used separately for molecular dynamics (MD) simulations alone and in complex with the repurposed drug, rutin. All the four MD simulations were executed through GROMACS v5.0 under the force field GROMOS96 54a7 having water model SPC216 along with the time step of 1 fs for 100 ns (Abraham et al., 2015; Darden et al., 1993). Varied sizes of the simulation box were created for each MD simulation event, which were further loaded with about respective amount of water molecules using the SPC model. The total charge on spike protein, main protease and the two in complex with rutin were neutralized by adding –6, –4, –6, and –4 charges, respectively, and were incorporated into the simulation system by compensating the water molecules in the arbitrary locations inside the simulation box. The NPT ensembles, along with periodic boundary conditions, were utilized to carry out MD simulations. A cut-off of about 12 Å was used in order to manage the Vander Waals forces. The Particle Mesh Ewald model manifesting a cut-off of 14 Å was further utilized to calculate the electrostatic interactions (Darden et al., 1993). The spike protein, main protease and the two in complex with rutin were solvated through a slab of about 10 Å in every direction. The neighbor list was updated to a frequency of 10 ps.