Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26

Naveen Vankadari, Jacqueline A Wilce, Naveen Vankadari, Jacqueline A Wilce

Abstract

The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics.

Keywords: CD26; Coronavirus; docking; glycosylation; spike glycoprotein.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Overall homo-trimer model structure of the COVID-19 spike glycoprotein (A) ligand unbound conformation (B) ligand-bound conformation. The three protomers are coloured pink, green and cyan. S1- and S2- domains labelled. Receptor-binding induced hinge motion of S1 is distinguishable. (C) Predicted Glycan shield (spheres) of COVID-19 (green) and SARS-CoV (blue) spike glycoproteins. predicted 3C-like proteinase cleavage site (yellow). Predicted N-linked glycosylation sites for COVID-19 (D) and SARS-CoV (E). Unique glycosylation sites are coloured in Blue, and shared sites are shaded in Red.
Figure 1.
Figure 1.
Overall homo-trimer model structure of the COVID-19 spike glycoprotein (A) ligand unbound conformation (B) ligand-bound conformation. The three protomers are coloured pink, green and cyan. S1- and S2- domains labelled. Receptor-binding induced hinge motion of S1 is distinguishable. (C) Predicted Glycan shield (spheres) of COVID-19 (green) and SARS-CoV (blue) spike glycoproteins. predicted 3C-like proteinase cleavage site (yellow). Predicted N-linked glycosylation sites for COVID-19 (D) and SARS-CoV (E). Unique glycosylation sites are coloured in Blue, and shared sites are shaded in Red.
Figure 2.
Figure 2.
(A and B) Ribbon and a surface diagram showing the docking interface of modelled COVID-19 (grey) and human CD26 (orange)(PDB: 4QZV) complex. Predicted key residues involved in the interaction are shown in sticks (CD26 residues are underlined) (C) Overall docking results showing the surface model of CD26 with COVID-19 predicted homo-trimer structure (ligand-bound conformation).
Figure 2.
Figure 2.
(A and B) Ribbon and a surface diagram showing the docking interface of modelled COVID-19 (grey) and human CD26 (orange)(PDB: 4QZV) complex. Predicted key residues involved in the interaction are shown in sticks (CD26 residues are underlined) (C) Overall docking results showing the surface model of CD26 with COVID-19 predicted homo-trimer structure (ligand-bound conformation).

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Source: PubMed

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