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

Human noroviruses infect the gastrointestinal tract and are a leading cause of acute gastroenteritis worldwide. Common symptoms of norovirus include diarrhea, vomiting, and stomach cramps. Virus shedding and symptoms are prolonged and debilitating in immunocompromised patients. Currently, there are no approved vaccines or targeted antivirals for treating human norovirus infection. Human intestinal enteroids derived from intestinal stem cells allow the successful replication of norovirus in the laboratory and can be used as a physiologically relevant model system to evaluate antivirals. We discovered that 2'-fucosyllactose (2'FL), an oligosaccharide naturally occurring in human milk, inhibits GII.4 norovirus replication in HIEs from multiple donors and thus has the potential to be developed as a therapeutic for human norovirus. These findings have high translational potential since 2'FL from several manufacturers has a "generally recognized as safe" status and can be synthesized on a large scale for immediate application.