Results
Docking studies conclude the interaction of drugs with protein and residues involved in this complex. For such interaction studies, the most important condition was the proper orientation and conformation of drugs which fitted to the protein binding site appropriately and formed the protein-drug complex. Therefore, optimal interactions and docking results were defined. Docking and MD simulations were used in the molecular modeling protocol which accepted that the ASN479 group could have favorable interactions in the S1 subunit of SARS-CoV-2 spike protein.
Molecular modeling found the orientation with plots that were shown in Figure 1, where the ASN residue 479 was placed to interact with drugs. In this position, the asparagine of the SARS-CoV-2 spike protein is close to the residues that were connected by hydrophobic interactions and hydrogen bonds. In Anakinra drug, TYR442, TRP476, LEU478, LYS439, and ASP480 were contributed in addition to ASN479 by hydrophobic interactions (figure 2-a). In chloroquine drug, TYR440, ASP480, LEU478, and TYR442 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-b). In comostat drug, LEU478, ASP480, and TYR440 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-c). In favipiravir drug, TYR442, TYR440, and LEU478 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-d). In lamivudine drug, TYR442, TYR440, and ASP480 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-e). In losartan drug, TYR440, ASP480, LEU478, and TYR442 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-f). In the ribavirin drug, TYR440, ASP480, LEU478, and TYR442 were contributed in addition to ASN479 by hydrophobic interactions (Figure 2-h). Also it was shown with LigPlot software that drugs (b, c, d, e, f, and h) have hydrogen bonds with the protein in addition to. However, Orientations of this residues with drugs were approved by autodock vina (figure 1).
Table1: Binding energy between SARS-CoV-2 spike protein and drugs.
There are many similarities of SARS-CoV-2 with the original SARS-CoV. Using computer modeling it was found that the spike proteins of SARS-CoV-2 and SARS-CoV have almost identical 3-D structures in the receptor-binding domain that maintains van der Waals forces [13]. Therefore interactions of hydrophobic were concluded to treatment.
Fig 1. The plots generated by autodock vina software. These interactions are complex between SARS-CoV-2 spike protein complex; a) anakinra (binding energy=-7.4 kcal/mol), b) chloroquine (binding energy=-7.2 kcal/mol), c) comostat (binding energy=-8.8 kcal/mol), d) favipiravir (binding energy=-5 kcal/mol), e) lamirudine (binding energy=-6 kcal/mol), f) lostartan (binding energy=-6.7 kcal/mol), g) pepstatin (binding energy=-9.5 kcal/mol), h) ribavirin (binding energy=-6.9 kcal/mol).
Fig 2. The plots generated by LigPlot+ program. Hydrogen binding (blue line) and hydrophobic interactions ( red line) pockets of SARS-CoV-2 spike protein: drugs complexes; a) anakinra, b) chloroquine, c) comostat, d) favipiravir, e) lamivudine, f) losartan and h) ribavirin.