Structural basis for human coronavirus attachment to sialic acid receptors

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Coronavirus Infections / metabolism*
  • Coronavirus Infections / virology
  • Coronavirus OC43, Human / chemistry
  • Coronavirus OC43, Human / physiology*
  • Cryoelectron Microscopy
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • N-Acetylneuraminic Acid / analogs & derivatives
  • N-Acetylneuraminic Acid / metabolism*
  • Protein Multimerization
  • Receptors, Cell Surface / metabolism*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Internalization


  • Receptors, Cell Surface
  • Spike Glycoprotein, Coronavirus
  • sialic acid receptor
  • N-Acetylneuraminic Acid