Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides

Stefan Weichert; Anna Koromyslova; Bishal K Singh; Satoko Hansman; Stefan Jennewein; Horst Schroten; Grant S Hansman

doi:10.1128/JVI.03223-15

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.

Authors

Stefan Weichert¹, Anna Koromyslova^{2

3}, Bishal K Singh^{2

3}, Satoko Hansman^{1

2}, Stefan Jennewein⁴, Horst Schroten¹, Grant S Hansman^{5

3}

Affiliations

¹ Pediatric Infectious Diseases Unit, University Children's Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
² Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg, Germany.
³ Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany.
⁴ Jennewein Biotechnologie GmbH, Rheinbreitbach, Germany.
⁵ Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg, Germany g.hansman@dkfz.de.

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

Grants and funding

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).