Advances in Mini Gut Organoid Models Reveal Key Insights into Norovirus Replication
Sasirekha Ramani, PhD on creating a broad-spectrum antiviral that could be effective in various clinical settings, especially given the emergence of new and more dominant strains.
A recent study published in the Journal of Virology suggests that 2′-fucosyllactose (2′FL), a sugar found in human breast milk, may provide a new treatment for human norovirus (HuNoV), a leading cause of gastroenteritis. The study focused on the GII.4 Sydney [P16] strain of HuNoV and found that 2′FL could block the virus from entering and replicating in lab-grown human intestinal models.
In an exclusive interview with Sasirekha Ramani, PhD, a key researcher in the study, she discussed the ongoing efforts to develop a sugar-based treatment for norovirus. She explained that while the GII.4 strain has been the dominant strain of norovirus for about a decade, there has been a recent surge in outbreaks and hospitalizations, potentially linked to a new strain that has emerged and overtaken the older one.
"We definitely want to approach this from the perspective of: will this work against a broad array of strains?" Ramani explained. "Because unless you're at a large academic medical center, you typically don’t know which specific strain a person has—just whether or not they have norovirus. You’d want something that would be effective against multiple strains."
"These mini gut models are a really cool tool to study it. They’ve only been published in the last 10 years, but before that, the only way to study norovirus was by conducting controlled human infection studies," she said. "We have controlled human infection studies for three different strains of norovirus, so we could go from the lab to controlled human infection studies to determine dosing and other parameters."
Ramani emphasized that this research is still in its early stages but that the novel approach—targeting the virus's biology rather than just viral enzymes like proteases or polymerases—holds great potential. She also noted the encouraging results from testing 2′FL in organoid models made from cells of different individuals. "One of the exciting things we were able to do was test it in organoids from the same person, but from different segments. This way, we could eliminate host genetics as a factor and just focus on which segment of the gut the virus replicates in. The nice thing is, it worked across all segments."
Despite these promising results, Ramani acknowledged there is still work to be done. "Even though we tested it in 10 different organoid lines—from 10 different people—it did not completely inhibit the virus replication in every person. So, there’s more to be done."
Listen to the first part of our interview, Ramani explained that 2′FL effectively reduced norovirus replication in older children and adults but not in infants, due to lower levels of key sugars in their cells. She highlighted its novel mechanism as a "decoy receptor," blocking the virus from binding to human cells and offering a potential new approach to antiviral treatments, especially for vulnerable populations: https://www.contagionlive.com/view/human-milk-sugar-blocks-norovirus-in-lab-models
