{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:24:58Z","timestamp":1786973098934,"version":"build-2736575974"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["P30 DK056338"],"award-info":[{"award-number":["P30 DK056338"]}]},{"name":"HHS | National Institutes of Health","award":["P01 AI 057788"],"award-info":[{"award-number":["P01 AI 057788"]}]},{"name":"HHS | National Institutes of Health","award":["S10 OD028480"],"award-info":[{"award-number":["S10 OD028480"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,2,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2\u2032-fucosyllactose (2\u2032FL) in the same pocket as HBGAs for some HuNoV strains. We evaluated the effect of 2\u2032FL on the replication of a globally dominant GII.4 Sydney [P16] HuNoV strain using human intestinal enteroids (HIEs) from adults and children. A significant reduction in GII.4 Sydney [P16] replication was seen in duodenal and jejunal HIEs from multiple adult donors, all segments of the small intestine from an adult organ donor, and in two pediatric duodenal HIEs. However, 2\u2032FL did not inhibit HuNoV replication in two infant jejunal HIEs that had significantly lower expression of \u03b11\u20132-fucosylated glycans. 2\u2032FL can be synthesized in large scale, and safety and tolerance have been assessed previously. Our data suggest that 2\u2032FL has the potential to be developed as a therapeutic for HuNoV gastroenteritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>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\u2032-fucosyllactose (2\u2032FL), 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\u2032FL from several manufacturers has a \u201cgenerally recognized as safe\u201d status and can be synthesized on a large scale for immediate application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00938-24","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T09:00:20Z","timestamp":1736499620000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["2\u2032-Fucosyllactose inhibits human norovirus replication in human intestinal enteroids"],"prefix":"10.1128","volume":"99","author":[{"given":"Ketki","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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