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Nat Struct Mol Biol. 2019 Jun;26(6):481-489. doi: 10.1038/s41594-019-0233-y. Epub 2019 Jun 3.

Structural basis for human coronavirus attachment to sialic acid receptors.

Author information

1
Department of Biochemistry, University of Washington, Seattle, WA, USA.
2
Institut Pasteur, Unité de Virologie Structurale, Paris, France.
3
CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
4
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
5
Department of Chemical Biology and Drug Discovery, Utrecht University, Utrecht, the Netherlands.
6
Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
7
Department of Chemistry, University of Georgia, Athens, GA, USA.
8
Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
9
Department of Biochemistry, University of Washington, Seattle, WA, USA. dveesler@uw.edu.

Abstract

Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We show that the ligand binds with fast kinetics to a surface-exposed groove and that interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide does not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to those of the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.

PMID:
31160783
PMCID:
PMC6554059
DOI:
10.1038/s41594-019-0233-y
[Indexed for MEDLINE]
Free PMC Article

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