Fig 1.
The co-crystallized ligands of SARS-Cov-2 proteins and Quercetin.
Table 1.
Structural properties of Quercetin with the co-crystallized ligands of SARSCoV-2 proteins.
Fig 2.
The analysis of similarity between the co-crystallized ligands of SARS-CoV-2 proteins and Quercetin (green ball) revealed notable parallels with Remdesivir (red ball).
Fig 3.
The 3D-flexible alignment of Quercetin (depicted in green) with Remdesivir (shown in blue).
Fig 4.
Interactions of Remdesivir in the active site of the RdRp A) 3D form and B) 2D form. C) The comparison of binding modes of docked (in green) and original (in cyan) co-crystallized ligand (Remdesivir).
Fig 5.
3D, 2D, and Surface mapping interactions of Quercetin in the active site of the RdRp.
Fig 6.
3D superimposition of Quercetin and Remdesivir in the active site of RNA-dependent RNA polymerase of SARS-CoV-2.
Fig 7.
Analysis performed on the RdRp-Quercetin complex.
A) Distance from the center of mass of Quercetin to RdRp, B) Quercetin RMSD, C) RdRp RMSD, D) the complex RMSD, E) protein RMSF based on the Carbon alpha atoms, F) Radius of Gyration for the protein, G) change in the number of H-bonds, H) the change in the SASA values.
Fig 8.
Analysis performed on the RdRp-Remdesivir complex.
A) Distance from the center of mass of Remdesivir to RdRp, B) Remdesivir RMSD, C) RdRp RMSD, D) the complex RMSD, E) protein RMSF based on the Carbon alpha atoms, F) Radius of Gyration for the protein, G) the change in the SASA values, H) change in the number of H-bonds.
Fig 9.
The energetic parameters obtained from MM-GBSA investigations, along with their respective numerical values, while the bars indicate the standard deviations associated with each measurement.
Fig 10.
The breakdown of binding free energies for the complexes involving RdRp-Quercetin and RdRp-Remdesivir.
Fig 11.
The amino acids grouped according to their interactions with A) Remdesivir (occurring in at least 50% of cases) and B) Quercetin (occurring in at least 75% of cases).
Additionally, it presents their occurrence frequency throughout the entire simulation period, employing the ProLIF Python library.
Fig 12.
The interactions stemming from representative clusters identified by TTClust and their three-dimensional interactions with Quercetin.
Grey dashed lines represent hydrophobic interactions, and blue solid lines depict hydrogen bonds. Quercetin is depicted using orange sticks, while the amino acids of the RdRp protein involved in these interactions are represented by blue sticks.
Fig 13.
The interactions stemming from representative clusters identified by TTClust and their three-dimensional interaction with Remdesivir.
Dashed grey lines represent hydrophobic interaction, dashed yellow lines denote salt bridges, and solid blue lines depict hydrogen bonds. Remdesivir is depicted using orange sticks, while the amino acids of the RdRp protein involved in these interactions are represented by blue sticks.
Fig 14.
The change in eigenvalues with the increasing of the number of eigenvectors (blue), while the red line illustrates the cumulative variance retained by the eigenvectors.
Fig 15.
The cosine content values of the first ten eigenvectors for the two trajectories of the RdRp-Quercetin and RdRp-Remdesivir complexes.
Fig 16.
The projection of the RdRp-Quercetin and RdRp-Remdesivir trajectories.
A) displays the first and third eigenvectors, B) shows the second and third eigenvectors, and C) depicts the PC1-PC2-PC3. In the plots, small dots transitioning from white to black represent frames from the RdRp-Remdesivir simulation, while dots changing from white to red represent frames from the RdRp-Quercetin simulation.
Fig 17.
Dose-response curves of RdRp activity inhibition by Quercetin (A) Remdesivir (B).
Fig 18.
The dose-response curves of Quercetin (A) and Remdesivir (B) against SARS-CoV-2 and their CC50 (μg/mL) values.
All data are presented as mean ± SD, with n = 3 replicates.