OmniVira

Structural basis for human coronavirus attachment to sialic acid receptors.

M Alejandra Tortorici1,2,3 Alexandra C Walls1 Yifei Lang4 Chunyan Wang4 Zeshi Li5,6 Danielle Koerhuis4 Geert-Jan Boons5,6,7,8 Berend-Jan Bosch4 Félix A Rey2,3 Raoul J de Groot4 David Veesler9
Affiliations 9 institutions
  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. [email protected].
PMID31160783 DOI10.1038/s41594-019-0233-y Year2019 Journal Nature structural & molecular biology Nat Struct Mol Biol Languageeng Statusppublish

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.

Supporting text Virus Host Location
Coronavirus Infections 171 Coronavirus OC43, Human 7 Cryoelectron Microscopy 37 HEK293 Cells 61 Humans 1440 Models, Molecular 99 N-Acetylneuraminic Acid 25 Protein Multimerization 4 Receptors, Cell Surface 28 Spike Glycoprotein, Coronavirus 274 Virus Internalization 100 sialic acid receptor 14

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE11544 Receptor Usage
Key finding

Human coronavirus OC43 spike glycoprotein binds 9-O-acetylated sialic acid through a defined groove that is essential for viral entry.

Virus
human coronavirus OC43
Host
human Homo sapiens Experimental system host cells Experimental system
Location
Not specified
Supporting text

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.

Method
cryo-EM structure determination | ligand binding assay | viral entry functional analysis
Receptors
9-O-acetylated sialic acid