Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides

J Virol. 2016 Apr 14;90(9):4843-4848. doi: 10.1128/JVI.03223-15. Print 2016 May.

Abstract

Histo-blood group antigens (HBGAs) are important binding factors for norovirus infections. We show that two human milk oligosaccharides, 2'-fucosyllactose (2'FL) and 3-fucosyllactose (3FL), could block norovirus from binding to surrogate HBGA samples. We found that 2'FL and 3FL bound at the equivalent HBGA pockets on the norovirus capsid using X-ray crystallography. Our data revealed that 2'FL and 3FL structurally mimic HBGAs. These results suggest that 2'FL and 3FL might act as naturally occurring decoys in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Blood Group Antigens / chemistry
  • Blood Group Antigens / metabolism
  • Crystallography, X-Ray
  • Humans
  • Milk, Human / chemistry*
  • Models, Molecular*
  • Molecular Conformation*
  • Norovirus / drug effects*
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Structure-Activity Relationship
  • Trisaccharides / chemistry
  • Trisaccharides / pharmacology

Substances

  • Antiviral Agents
  • Blood Group Antigens
  • Oligosaccharides
  • Trisaccharides
  • 3'-fucosyllactose
  • 2'-fucosyllactose

Grant support

Funding for this study was also provided to Anna Koromyslova and Grant Hansman by the CHS Foundation, the Helmholtz-Chinese Academy of Sciences (HCJRG-202).