Abstract
Norovirus infections belong to the most common causes of human gastroenteritis worldwide, and epidemic outbreaks are responsible for hundreds of thousands deaths annually. Strikingly, no antiviral treatment is available due to the difficulty in cultivating virions or in generating a vaccine, and due to the fact that their infection mechanisms are poorly understood. However, there is consent that noroviruses bind to histo-blood group antigens (HBGAs) on their way through the digestive tract. The HBGA profiles vary individually, making people more or less susceptible to different norovirus strains. In our current work, we tried to decipher the HBGA specificity of the most prevalent and clinically relevant norovirus GII.4 subfamily (Sydney 2012, JX459908) and its preferences for human milk oligosaccharides (HMOs) as potential anti-infectives. The structural evidence provided can explain at the molecular level why individuals with certain blood groups are at higher risk of infection, and how these infections may be prevented and treated by application of food additives. A central finding was that low-affinity binding of HMOs is surpassed by high-avidity binding of multivalent oligo- and polyfucoses as found in algal polysaccharides (fucoidans). Insight into structural details of fucoidans and their impact on noroviral-blocking efficiency is provided and discussed.
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