The Groundbreaking NUS Discovery: Levan from Bacillus subtilis CU1
Researchers at the National University of Singapore (NUS) have made a significant advance in combating norovirus, the leading cause of acute gastroenteritis worldwide. A team from the Department of Food Science and Technology, led by Associate Professor Dan Li, identified levan—a natural exopolysaccharide produced by the probiotic bacterium Bacillus subtilis CU1—as a potent inhibitor of human norovirus infection. This compound works by binding directly to the virus particles, creating a physical barrier that prevents them from attaching to and infecting host cells.
Published in Food Microbiology in October 2025, the study highlights levan's specificity for the GII.4 strain, which is responsible for the majority of global norovirus outbreaks. Unlike antiviral drugs that destroy the virus or vaccines that stimulate immunity, levan offers a preventive shield active at the earliest stage of infection, making it particularly promising for vulnerable populations such as the elderly, young children, and immunocompromised individuals.
Assoc Prof Li Dan emphasized the potential impact: "Our findings show that it is possible to block the virus before it can establish an infection. This could be especially useful for people who cannot rely on strong immune responses." This innovation builds on NUS's prior breakthrough in 2023, when the same team developed a zebrafish embryo model for cultivating human norovirus, overcoming a long-standing challenge in virology research.
Norovirus: A Global and Singaporean Public Health Challenge
Norovirus, often called the "stomach flu" or "winter vomiting bug," is highly contagious, spreading through contaminated food, water, surfaces, or close contact. Globally, the World Health Organization estimates it causes 685 million cases annually, including 200 million in children under five, leading to around 200,000 deaths, primarily among young children in low-income settings. Symptoms include sudden vomiting, diarrhea, nausea, and stomach cramps, lasting 1-3 days but capable of dehydrating patients rapidly.
In Singapore, foodborne diseases, including norovirus, impose a substantial economic burden, costing approximately S$80 million yearly in healthcare and productivity losses. Recent outbreaks in 2025 affected preschools and events, underscoring the need for preventive strategies in dense urban environments like schools, hospitals, and cruise ships—common hotspots for rapid spread. With no approved vaccines or antivirals, current management relies on hydration and hygiene, highlighting the urgency of NUS's research.
- High infectivity: As few as 18 viral particles can cause infection.
- Strain dominance: GII.4 accounts for most outbreaks due to antigenic drift.
- Singapore context: Frequent institutional outbreaks strain public health resources.
For academics and students in Singapore's higher education sector, such research exemplifies how university labs contribute to national resilience against infectious diseases. Explore opportunities in higher ed jobs at institutions like NUS driving these innovations.
How Levan Works: Step-by-Step Mechanism of Action
Levan, a β-(2,6)-linked polyfructose (fructan), is secreted by B. subtilis CU1 as an exopolysaccharide (EPS). Unlike live probiotics, which may pose risks for immunocompromised patients, levan is acellular and stable. The study demonstrated its efficacy through rigorous testing:
- Viral Binding: Levan exhibits high-avidity binding to GII.4 virus-like particles (VLPs) and P particles (protruding domains key for host attachment), confirmed via saliva-binding ELISA and bio-layer interferometry.
- Attachment Blockade: This physical interaction prevents norovirus from adhering to host cell receptors, halting entry without lysing the virus or triggering inflammation.
- Replication Inhibition: In the zebrafish model, levan significantly reduced GII.4 replication, with no effect on other strains like GII.2 or GII.17, indicating genotype specificity.
This non-immune mechanism offers broad applicability, potentially integrable into foods or sprays for high-risk settings. Read more in the full study: Food Microbiology paper.
Innovative Methodology: From Zebrafish Model to Carrot Juice Fermentation
NUS's research leveraged their proprietary zebrafish embryo/larva model, established in 2023, which consistently supports human norovirus replication—addressing the virus's historical uncultivability in labs. Initial screening used Tulane virus (a murine surrogate) on LLC-MK2 cells, followed by human strains (GII.4, GII.2, GII.17) in vivo.
EPS purification involved ethanol precipitation and anion-exchange chromatography, with structural analysis confirming levan as the active fraction. Scalability was demonstrated by fermenting carrot juice (5% w/v sucrose) with B. subtilis CU1, yielding high EPS levels while preserving antiviral activity—a food-grade, cost-effective approach ideal for functional beverages or supplements.
Collaborators included A*STAR's Singapore Institute for Food and Biotechnology Innovation, enhancing translational potential.
Assoc Prof Dan Li and NUS Food Science Excellence
Leading the charge is Assoc Prof Dan Li, whose lab at NUS's Department of Food Science and Technology (FST) specializes in food virology and probiotics. Her team's prior work on fucoidan (a seaweed polysaccharide) and zebrafish models positions NUS as a global leader in norovirus research. FST, part of the Faculty of Science, boasts state-of-the-art facilities and interdisciplinary ties, fostering innovations that bridge academia and industry.
Singapore's universities like NUS drive national priorities in food security and health. Aspiring researchers can find roles via university jobs in Singapore's vibrant higher ed scene. Explore Singapore academic opportunities.
Implications for Public Health and Higher Education
This discovery could transform norovirus prevention, especially in outbreak-prone Singapore institutions. Levan-supplemented products might protect cruise ships, schools, and hospitals. Economically, reducing S$80M foodborne costs aligns with Singapore's Smart Nation agenda.
- Preventive over therapeutic: Blocks infection pre-symptom.
- Safe for at-risk groups: No live microbes.
- Sustainable production: Carrot waste valorization.
For higher ed, it underscores NUS's role in translational research, attracting funding and talent. Check higher ed career advice for paths in food microbiology.
NUS News ReleaseChallenges Ahead and Future Outlook
While promising, challenges include long-term human trials, stability in products, and efficacy against emerging strains. NUS plans optimization for clinical translation, potentially partnering with A*STAR for commercialization.
Looking ahead, this paves the way for EPS-based antivirals against other pathogens. Singapore's research ecosystem, bolstered by NRF funding, positions NUS to lead. Students and profs eyeing research careers should rate faculty via Rate My Professor.
Career Opportunities in Food Virology at Singapore Universities
NUS's success highlights demand for experts in probiotics, virology, and biotech. Roles in faculty, postdocs, and research assistants abound. Visit higher ed faculty jobs, postdoc positions, or research assistant jobs for openings. Craft your academic CV to join this field.
Conclusion: NUS Paving the Way for Norovirus Prevention
The levan discovery exemplifies Singapore higher education's impact on global health. As norovirus remains a threat, NUS innovations offer hope. Stay informed on academic opportunities at Rate My Professor, search higher ed jobs, or get higher ed career advice. For university positions, browse university jobs or Singapore jobs.
Read the WHO overview: WHO Norovirus Factsheet.