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Literature detail

Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2.

Linh Nguyen1 Kelli A McCord1 Duong T Bui1 Kim M Bouwman2 Elena N Kitova1 Mohamed Elaish3,4 Dhanraj Kumawat1 Gour C Daskhan1 Ilhan Tomris2 Ling Han1 Pradeep Chopra5 Tzu-Jing Yang6 Steven D Willows7 Andrew L Mason7 Lara K Mahal1 Todd L Lowary1,6,8 Lori J West9,10 Shang-Te Danny Hsu6,8 Tom Hobman3,10 Stephen M Tompkins11,12 Geert-Jan Boons2,5,13,14 Robert P de Vries2 Matthew S Macauley15,16 John S Klassen17
Affiliations 17 institutions
  1. Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
  2. Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
  3. Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
  4. Poultry Disease Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  5. Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
  6. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
  7. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
  8. Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
  9. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
  10. Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
  11. Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
  12. Emory-UGA Centers of Excellence for Influenza Research and Surveillance (CEIRS), Athens, GA, USA.
  13. Department of Chemistry, University of Georgia, Athens, GA, USA.
  14. Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
  15. Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. [email protected].
  16. Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. [email protected].
  17. Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. [email protected].
PMID 34754101 2022 Nat Chem Biol eng ppublish
PubMed DOI Browse context

Article

Publication summary

Emerging evidence suggests that host glycans influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal that the receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind to the RBD. The monomeric affinities (K<sub>d</sub> = 100-200 μM) of gangliosides for the RBD are similar to another negatively charged glycan ligand of the RBD proposed as a viral co-receptor, heparan sulfate (HS) dp2-dp6 oligosaccharides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels using three approaches: sialyltransferase (ST) inhibition, genetic knockout of Sia biosynthesis, or neuraminidase treatment. These effects on RBD binding and both pseudotyped and authentic SARS-CoV-2 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.

Angiotensin-Converting Enzyme 2 Binding Sites Glycolipids Humans SARS-CoV-2 Sialic Acids Spike Glycoprotein, Coronavirus ACE2 protein, human spike protein, SARS-CoV-2

Structured evidence records

Evidence records

1 total
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.98
Key finding

SARS-CoV-2 spike RBD binds sialic acid–containing gangliosides and uses them as co-receptors to facilitate viral entry along with ACE2.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The receptor-binding domain (RBD) of the spike (S) protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (Sia), with preference for monosialylated gangliosides. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to angiotensin-converting enzyme 2 (ACE2)-expressing cells is decreased following depletion of cell surface Sia levels.

Method
pseudovirus assay; binding assay
Receptors
sialic acid
Host factors
ACE2