Table 1.
Summary table of designed primers for amplification and sequencing of hDPP4 gene exons 9, 10, 11 and 12.
Table 2.
Middle East respiratory syndrome coronavirus (MERS-CoV) study population demographics, dromedary exposure and serological profile by study group.
Fig 1.
Alignment of human and animal DPP4 protein sequences by Clustal W.
Identical amino acid residues in different species are highlighted with the same residue colour. Mutations identified in this study are highlighted in black.
Table 3.
Participants serological profile with identified mutations in amino acid residues engaging the interaction of DPP4 with MERS-CoV.
Table 4.
Statistical significance for association of sex, type of exposure and seropositivity with the presence of a mutation in the receptor DPP4 binding residues according to the Fisher and Risk Ratio test.
Table 5.
Assessment of the effect of human DPP4 mutations identified among the population study on protein-protein interaction (PPI) using computational prediction tools Mutabind2 and DynaMut.
Fig 2.
Cα-Backbone root mean square deviation (RMSD) of the human DPP4 protein in complex with MERS-CoV S1 RBD protein, during 150 ns of the molecular dynamics simulation period.
(a) RMSD 4L72-WT vs 4L72-N229I. (b) RMSD 4L72-WT vs 4L72-K267N. (c) RMSD 4L72-WT vs 4L72-K267E. (d) RMSD 4L72-WT vs 4L72-T288P. (e) RMSD 4L72-WT vs 4L72-L294V. (f) RMSD 4L72-WT vs 4L72-I295L.
Fig 3.
Cα-Backbone root mean square fluctuation (RMSF) of the human DPP4 protein in complex with MERS-CoV S1 RBD protein, during 150 ns of the molecular dynamics simulation period.
(a) RMSF 4L72-WT vs 4L72-N229I. (b) RMSF 4L72-WT vs 4L72-K267N. (c) RMSF 4L72-WT vs 4L72-K267E. (d) RMSF 4L72-WT vs 4L72-T288P. (e) RMSF 4L72-WT vs 4L72-L294V. (f) RMSF 4L72-WT vs 4L72-I295L.
Fig 4.
Cα-Backbone Radius of gyration (Rg) of the human DPP4 protein in complex with MERS-CoV S1 RBD protein, during 150 ns of the molecular dynamics simulation period.
(a) Rg 4L72-WT vs 4L72-N229I. (b) Rg 4L72-WT vs 4L72-K267N. (c) Rg 4L72-WT vs 4L72-K267E. (d) Rg 4L72-WT vs 4L72-T288P. (e) Rg 4L72-WT vs 4L72-L294V. (f) Rg 4L72-WT vs 4L72-I295L.
Fig 5.
Solvent accessible surface area (SASA) between MERS-CoV S1 RBD protein and human DPP4 wild and mutant types during 150 ns of the molecular dynamics simulation period.
(a) Rg 4L72-WT vs 4L72-N229I. (b) Rg 4L72-WT vs 4L72-K267N. (c) Rg 4L72-WT vs 4L72-K267E. (d) Rg 4L72-WT vs 4L72-T288P. (e) Rg 4L72-WT vs 4L72-L294V. (f) Rg 4L72-WT vs 4L72-I295L.
Fig 6.
Total number of hydrogen bonds interactions between MERS-CoV S1 RBD protein and human DPP4 wild and mutant types during 150 ns of the molecular dynamics simulation period.
(a) H-bond 4L72-WT vs 4L72-N229I. (b) H-bond 4L72-WT vs 4L72-K267N. (c) H-bond 4L72-WT vs 4L72-K267E. (d) H-bond 4L72-WT vs 4L72-T288P. (e) H-bond 4L72-WT vs 4L72-L294V. (f) H-bond 4L72-WT vs 4L72-I295L.
Fig 7.
Number of hydrogen bonds at the interface level of interacting residues of MERS-CoV S1 RBD protein and human DPP4 wild and mutant types during 150 ns of the molecular dynamics simulation period.
(a) H-bond 4L72-WT vs 4L72-N229I. (b) H-bond 4L72-WT vs 4L72-K267N. (c) H-bond 4L72-WT vs 4L72-K267E. (d) H-bond 4L72-WT vs 4L72-T288P. (e) H-bond 4L72-WT vs 4L72-L294V. (f) H-bond 4L72-WT vs 4L72-I295L.
Fig 8.
Principal component analysis 2-D projection MERS-CoV S1 RBD in complex with DPP4 wild and mutant type in phase space along first two principal eigenvectors.
(a) RMSD 4L72-WT vs 4L72-N229I. (b) RMSD 4L72-WT vs 4L72-K267N. (c) RMSD 4L72-WT vs 4L72-K267E. (d) RMSD 4L72-WT vs 4L72-T288P. (e) RMSD 4L72-WT vs 4L72-L294V. (f) RMSD 4L72-WT vs 4L72-I295L.
Fig 9.
Structural model of wild and mutant 4L72 models after 150 ns MD simulation.
Residues substituted are marked in red, residues involved in hydrophobic interactions are indicated in magenta, residues engaging simultaneous hydrogen bonding and hydrophobic contacts are indicated in green. DPP4 (chain A) and MERS-CoV S1 RBD protein (chain B) are dyed respectively with grey and blue. Ligands (NAG, BMA) are highlighted in pink. Hydrogen bonds are shown in black line and hydrophobic/ionic contacts are shown in yellow line.