German researchers believe they have found a relatively easy way to control the spread of norovirus, the most common cause of gastroenteritis worldwide. Their paper, published in the Journal of Biological Chemistry recently, details their efforts to find and develop a compound that could be used as a food supplement to stop the spread of norovirus in children’s hospitals.
Norovirus causes disease after entering cells in the gut by binding to fucose, which is found on cell surfaces. Norovirus can't tell the difference between fucoses that are part of cells in the gut and those that are simply passing through. For this reason, adding a fucose-based supplement to the diet as a decoy could be a way to capture the virus and keep it from infecting cells, according to the German team.
To develop this strategy, however, they needed to understand which features of fucose and virus molecules affected how well they attached to each other. In cells, foods, and milk, fucose is rarely found as a single molecule; rather, it's part of chains or networks of sugars and proteins. Franz-Georg Hanisch, a researcher at the University of Cologne, led a project to disentangle these molecular elements and understand what kind of fucose-based product would best to distract noroviruses. He started by screening the many types of fucose-containing human milk oligosaccharides (HMOs).
To Hanisch's surprise, the strength of the binding between the norovirus protein and HMOs did not depend much on the specific structure of the HMO, or the types of fucose molecules it contained. Rather, what mattered was only how many fucoses it contained. Each individual fucose stuck weakly to the virus protein, but the more fucoses there were in the compound, the better the compound and the viral protein stuck together.
"The binding of the virus is not dependent in any way on further structural elements of HMOs," Hanisch said. "It's only the terminal fucose which is recognized, and the more fucose at higher densities is presented, the better is the binding."
The researchers turned to brown algae, which produces fucoidan, a complex network of many fucoses. The organization of the fucose in fucoidans looks nothing like any fucose-containing molecules found in the human body, but fucoidan nevertheless tightly bound to the virus protein in the team's experiments, which meant that fucoidan could be a safe and cheap food additive to block viruses from infecting cells.
Hanisch and his collaborators are now focusing on experiments with live viruses and live organisms. The hope is to eventually have a fucose-based food supplement that could be given to a group of people, like hospitalized children, at the first sign of a norovirus outbreak, to prevent the circulating viruses from entering their cells and causing disease.