Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 20, 2025 8 hours, 6 minutes ago
Medical News: Human noroviruses (HuNoVs) are notorious as the leading cause of acute gastroenteritis worldwide, a condition characterized by diarrhea, vomiting, and abdominal pain. Affecting all age groups, norovirus outbreaks frequently occur in high-risk settings such as hospitals, long-term care facilities, cruise ships, and restaurants. Alarmingly, these infections are responsible for an estimated 677 million cases and over 200,000 deaths globally each year, primarily in low- and middle-income countries. Despite the heavy disease burden, effective treatments or vaccines for HuNoVs are not currently available. At present, the United States is facing one of the worse outbreaks of Norovirus across the country.
Human Milk Sugar Offers New Hope for Norovirus Treatment
The Potential Role of Human Milk Oligosaccharides
Human milk oligosaccharides (HMOs) have emerged as a promising area of research in the fight against enteric diseases. These naturally occurring sugars in human breast milk have been shown to block the attachment of various pathogens to human cells. Among these HMOs, 2′-fucosyllactose (2′FL) has attracted significant attention due to its structural similarity to histo-blood group antigens (HBGAs), the cellular receptors to which noroviruses bind.
This
Medical News report delves into groundbreaking research conducted by a team from Baylor College of Medicine and the University of California San Diego. Their study explores the potential of 2′FL to inhibit norovirus replication in human intestinal enteroids (HIEs), which are laboratory-grown intestinal cells that closely mimic the human gut environment.
Key Findings from the Study
The research team conducted an extensive series of experiments to evaluate the efficacy of 2′FL against the replication of the GII.4 Sydney [P16] strain of HuNoV, the globally dominant strain. Here are the study’s most significant findings:
-Reduction in Norovirus Replication
The study revealed that 2′FL significantly reduced norovirus replication in HIEs derived from adult and pediatric donors. When tested in HIEs from the duodenum and jejunum (parts of the small intestine), the researchers observed a remarkable reduction in viral replication, particularly at a concentration of 20 mg/mL of 2′FL. The effect was consistent across samples from multiple adult donors and intestinal segments, indicating the broad applicability of this treatment.
-Age and Segment Specificity
Interestingly, the inhibitory effect of 2′FL varied depending on the donor’s age and the intestinal segment. In adult and pediatric duodenal HIEs, 2′FL exhibited a robust antiviral effect. However, in infant jejunal HIEs, which had significantly lower expression of α1-2-fucosylated glycans, 2′FL did not inhibit viral replication. This suggests that the efficacy of 2′FL may depend on the presence of specific glycan receptors in the gut.
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Mechanism of Action
The study confirmed that 2′FL acts as a decoy receptor, mimicking HBGAs and thereby preventing the virus from attaching to and infecting human cells. X-ray crystallography studies have previously demonstrated that 2′FL binds to the same pocket on the viral capsid protein as HBGAs, further supporting its role as a competitive inhibitor.
Safety and Scalability
A key advantage of 2′FL is its safety and scalability. It can be synthesized in large quantities using bioengineering techniques and has already been classified as “Generally Recognized as Safe” (GRAS) by the U.S. Food and Drug Administration. Clinical trials in adults and infants have demonstrated that 2′FL is well-tolerated even at high doses, paving the way for its potential use as a therapeutic agent.
Implications for Public Health
The findings of this study are particularly significant given the lack of targeted antiviral treatments for HuNoV. If developed further, 2′FL could serve as an effective oral therapeutic for preventing and treating norovirus infections. Its potential applications range from outbreak control in high-risk environments to managing chronic infections in immunocompromised patients.
Conclusions
This research marks a major step forward in the quest for effective norovirus treatments. By demonstrating the antiviral properties of 2′FL in human intestinal cells, the study highlights the potential of this HMO to be developed into a safe and scalable therapeutic. While the inhibitory effects were not universal across all age groups and intestinal segments, the findings underscore the importance of targeted treatments tailored to specific populations.
Further research is needed to explore the use of 2′FL in combination with other HMOs or antiviral agents to enhance its efficacy. Additionally, clinical trials will be essential to determine the optimal dosage, safety, and long-term effects of 2′FL in humans. With continued investment and research, this discovery could revolutionize the management of norovirus infections and provide relief to millions worldwide.
The study findings were published in the peer-reviewed Journal of Virology.
https://journals.asm.org/doi/10.1128/jvi.00938-24
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