scholarly journals Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein

2017 ◽  
Vol 114 (40) ◽  
pp. E8508-E8517 ◽  
Author(s):  
Wentao Li ◽  
Ruben J. G. Hulswit ◽  
Ivy Widjaja ◽  
V. Stalin Raj ◽  
Ryan McBride ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Middle East ◽  
Cell Surface ◽  
Human Erythrocytes ◽  
Middle East Respiratory Syndrome ◽  
Host Cells ◽  
Dromedary Camel ◽  
Differential Distribution ◽  
Neuraminidase Treatment ◽  
Intact Virus

Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1A through S1D. Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B. We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A. When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus–Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.

scholarly journals Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2

2021 ◽  
Author(s):  
Linh Nguyen ◽  
Kelli McCord ◽  
Duong Bui ◽  
Kim Bouwman ◽  
Elena Kitova ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Receptor Binding ◽  
Viral Entry ◽  
Receptor Binding Domain ◽  
Artificial Membrane ◽  
Neuraminidase Treatment ◽  
S Protein ◽  
Knock Out

Abstract Emerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal that the receptor-binding domain (RBD) of the spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for the oligosaccharide of monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind the RBD. The monomeric affinities (Kd = 100-200 μM) of gangliosides for the RBD are similar to heparan sulfate, another negatively charged glycan ligand of the RBD proposed as a viral co-receptor. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to ACE2-expressing cells is decreased upon depleting cell surface SA level using three approaches: sialyltransferase inhibition, genetic knock-out of SA biosynthesis, or neuraminidase treatment. These effects on RBD binding and pseudotyped viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.

scholarly journals Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells

2018 ◽  
Vol 293 (30) ◽  
pp. 11709-11726 ◽  
Author(s):  
Hin Chu ◽  
Che-Man Chan ◽  
Xi Zhang ◽  
Yixin Wang ◽  
Shuofeng Yuan ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Host Cells ◽  
Bat Coronavirus

Electrophoretic and Chemical Characterization of the Charged Groups at the Surface of Murine CL3 Ascites Leukaemia Cells

1969 ◽  
Vol 4 (2) ◽  
pp. 289-298
Author(s):  
P. D. WARD ◽  
E. J. AMBROSE
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Chemical Characterization ◽  
Surface Protein ◽  
Subsequent Treatment ◽  
Surface Proteins ◽  
Carboxyl Groups ◽  
Neuraminidase Treatment ◽  
Ionic Nature ◽  
Ph Range

The electrophoretic characteristics of the murine CL3 ascites tumour were investigated. Treatment of the cells with formaldehyde raised the electrophoretic mobility (E.P.M.) from - 1.06 to - 1.28 µ/sec/V/cm; subsequent treatment with diazomethane reduced their mobility to zero. The E.P.M. of the diazomethane-treated cells did not alter over the pH range 3.0-8.0. This proved that the only ionic groups at this cell surface were amino and carboxyl groups. The absence of phosphate groups, another possibility, was confirmed by the lack of calcium-ion binding from 10 mM Ca2+ solutions. Neuraminidase treatment reduced the E.P.M. from -1.06 to -0.55 µ/sec/V/cm and free sialic acid was identified in the enzyme supernatant. Subsequent treatment of the cells with formaldehyde raised the mobility to -1.22 µ/sec/V/cm indicating that the change in E.P.M. on neuraminidase treatment was not due solely to the removal of the carboxyl groups of sialic acid but also to a change in the ionic nature of the surface. This change is ascribed to a change in the conformation of the surface protein. The reason for this change and a suggestion for the possible role of sialic acid at the cell surface are mentioned. Treatment of the cells with trypsin did not affect the viable cells in any way, suggesting that the surface proteins lack the basic amino acids lysine and arginine. Pronase treatment served only to show that much of the sialic acid was bound to protein; the total amount was not determined.

scholarly journals Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus Isolated from a Dromedary Camel in Egypt

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Ahmed Kandeil ◽  
Mahmoud M. Shehata ◽  
Rabeh El Shesheny ◽  
Mokhtar R. Gomaa ◽  
Mohamed A. Ali ◽  
...  
Keyword(s):  
Middle East ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Middle East Respiratory Syndrome ◽  
Full Genome Sequence ◽  
Dromedary Camel ◽  
Full Genome ◽  
High Similarity ◽  
Nasal Sample

We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.

scholarly journals Longitudinal study of Middle East Respiratory Syndrome coronavirus infection in dromedary camel herds in Saudi Arabia, 2014–2015

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Maged Gomaa Hemida ◽  
Abdulmohsen Alnaeem ◽  
Daniel KW Chu ◽  
Ranawaka APM Perera ◽  
Samuel MS Chan ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Longitudinal Study ◽  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Dromedary Camel ◽  
Coronavirus Infection

scholarly journals Changes in the random distribution of sialic acid at the surface of the myeloid sinusoidal endothelium resulting from the presence of diaphragmed fenestrae.

1979 ◽  
Vol 82 (3) ◽  
pp. 708-714 ◽  
Author(s):  
P P De Bruyn ◽  
S Michelson
Keyword(s):  
Endothelial Cell ◽  
Sialic Acid ◽  
Cell Surface ◽  
Random Distribution ◽  
Colloidal Iron ◽  
Neuraminidase Treatment ◽  
Endothelial Cell Surface ◽  
Anionic Charge ◽  
Sinusoidal Endothelium ◽  
Ph Range

Diaphragmed fenestrae (DF) are sites of increased vascular permeability. The anionic charge distribution at the luminal aspect of the DF of the endothelium of the bone marrow vessels has been studied after aldehyde fixation by means of colloidal iron (CI), native ferritin (NF), and polycationic ferritin (PCF). At pH 1.8, these cationic agents are bound by the nonmodified luminal endothelial cell surface but not at the sites of the DF. PCF was used over a pH range of 1.8--7.2 (CI is unstable at higher pH levels, whereas NF which has a pI of 4.5 is anionic above this point). PCF shows increased binding at the DF from pH 3.5 upwards. PCF binding at pH 1.8 at the nonmodified luminal cell surface is significantly diminished by neuraminidase treatment which, however, does not perceptibly reduce PCF binding at the higher pH levels. It is concluded that there are exposed sialic acid groups at the lunimal cell surface which are absent or significantly fewer at the sites of the DF, whereas other anionic materials possibly with a pKa higher than that of sialic acid (pKa 2.6) are present both at the DF and at the nonmodified endothelial cell surface.

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