2'-Fucosyllactose inhibits human norovirus replication in human intestinal enteroids

Area of Science:

• Virology and Gastroenterology
• Microbiome and Immunology

Background:

• Human noroviruses (HuNoVs) are a primary cause of acute gastroenteritis globally, with no specific antiviral treatments available.
• Cellular attachment factors, histo-blood group antigens (HBGAs), are crucial for HuNoV infection.
• Human milk oligosaccharides (HMOs), like 2 extquotesingle-fucosyllactose (2 extquotesingleFL), mimic HBGAs and can act as decoy receptors.

Purpose of the Study:

• To evaluate the antiviral potential of 2 extquotesingleFL against a prevalent GII.4 Sydney [P16] HuNoV strain.
• To assess the efficacy of 2 extquotesingleFL using human intestinal enteroids (HIEs) as a model system.

Main Methods:

• Utilized human intestinal enteroids (HIEs) derived from adult and pediatric donors.
• Exposed HIEs to the GII.4 Sydney [P16] HuNoV strain in the presence of 2 extquotesingleFL.
• Quantified viral replication and assessed glycan expression (specifically α1-2-fucosylated glycans).

Main Results:

• Significant reduction in GII.4 Sydney [P16] HuNoV replication was observed in most adult and pediatric HIEs.
• Inhibition was correlated with the expression of α1-2-fucosylated glycans.
• Two infant jejunal HIEs with low expression of these glycans showed no significant inhibition.

Conclusions:

• 2 extquotesingleFL demonstrates potential as a therapeutic agent for human norovirus gastroenteritis.
• The efficacy of 2 extquotesingleFL is dependent on the presence of specific fucosylated glycans in the intestinal epithelium.
• Large-scale synthesis and established safety of 2 extquotesingleFL support its translational potential.