Structural Basis for Human Milk Oligosaccharides Recognition by Evolutionarily Dominant Norovirus Genogroup II Genotypes

Fucosylated human milk oligosaccharides bind strongly to the P domain of latent norovirus genotypes GII.4 and GII.17, with NMR-derived dissociation constants of 20–33 mM.

• Why it matters: HMOs can act as soluble decoys against norovirus attachment, but the molecular rules for how different genotypes recognize specific HMO motifs remain unclear.
• What they did: The study combined STD NMR screening of 12 HMOs, NMR chemical shift perturbation titrations, and X-ray crystallography using the VP1 P domain from latent GII.2, dominant GII.4, and emerging GII.17.
• The result: GII.4 and GII.17 showed binding only for fucosylated HMOs, while GII.2 had little or no detectable binding; crystal structures indicate fucose anchoring and genotype-specific secondary contacts shaped by divergent loops.

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