Human Milk Sugar Blocks Norovirus in Lab Models
Sasirekha Ramani, PhD, discusses the potential of 2′FL as a treatment for norovirus and what more research could reveal.
A recent study in the Journal of Virology suggests that 2′-fucosyllactose (2′FL), a sugar found in human breast milk, may offer a treatment for human norovirus (HuNoV), a leading cause of gastroenteritis. The study focused on the GII4 Sydney (P16) strain of HuNoV, found that 2′FL can block the virus from entering and replicating in lab-grown human intestinal models.
Human norovirus, responsible for widespread vomiting and diarrhea, currently lacks targeted antiviral treatments. The virus binds to cells in the gut using histo-blood group antigens (HBGAs), which are similar to 2′FL. This structural similarity allows 2′FL to potentially block the virus from attaching to cells.
Researchers at Baylor College of Medicine tested 2′FL using human intestinal enteroids (HIEs), 3D models of the human gut. The study was led by Sasirekha Ramani, PhD, assistant professor of molecular virology and microbiology at Baylor, whose lab studies intestinal infections and works on developing treatments for viruses like norovirus and rotavirus.
Ramani explained the study’s significance, “We primarily work with rotavirus, which is a major cause of pediatric gastroenteritis, and norovirus, which affects all age groups. We aim to find ways to improve responses to these infections through translational studies—research that can directly inform public health strategies and clinical treatments.”
Ramani provided insight into the study's discrepancy: “We tested this particular sugar, two fucose, lactose, or 2′FL, against norovirus infectivity in organoids from many different age groups. And surprisingly, it did not work in the youngest infants, our babies, who were about two months old, and they were also preterm infants.”
She explained that the reason for this was that infant-derived HIEs had lower levels of α1–2-fucosylated glycans, which are crucial for HuNoV to attach to intestinal cells. Ramani added: “We found lower levels of these fucosylated sugars in the organoids from babies, but the virus replicates just as well, so we wonder whether there are additional attachment factors in babies, which is why the virus is able to replicate even when you're trying to block with this particular sugar.”
Despite this, the research still showed promising results for older children and adults. Ramani noted, “At 20 milligrams per milliliter, we saw a significant reduction in viral replication in organoids from all different age groups, except for the youngest infants. Perhaps for the youngest babies, we need to go higher, or maybe combinations of sugars are needed.”
2′FL works differently from traditional antiviral drugs, which often target the viral proteins responsible for replication. Ramani explained, “What it's really doing is acting like a decoy receptor. The virus binds to attachment factors on cells before it binds to those real attachment factors. Since this molecule is so similar, it essentially binds the virus and blocks its binding to its bona fide receptors on cells."
In addition to studying norovirus and rotavirus, Ramani’s team also investigates how human milk oligosaccharides (HMOs), like 2′FL, can influence viral infections. “Human milk sugars are an important part of early nutrition, and they have been shown to have protective effects against infections, including norovirus. In our research, we are particularly interested in how these sugars can be leveraged for therapeutic purposes,” Ramani explained.
While the study found 2′FL to be effective in adult and older pediatric models, more research is needed to understand its potential for infant populations. Ramani pointed out that “we may need higher concentrations of 2′FL or combinations of different human milk sugars to see the desired effect in babies.”
Ramani concluded, “This study opens the door to more research into human milk sugars as a novel antiviral treatment. With further investigation, we may find new ways to protect individuals from the widespread and often debilitating effects of norovirus.”
