(GlycoNoVi) Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies

Project summary

Glycans are carbohydrate structures ubiquitously found on the surface of cells and take part in many biological processes, including cell signaling and neoplasia. Research on glycans is challenging in part due to the limited availability of biologically relevant synthetic glycans and to technical challenges in the analysis of glycan-protein interactions. Glycans also exhibit key roles in viral infections, mediating virus attachment and entry. Human noroviruses (NoVs) are the major cause of viral gastroenteritis and foodborne illnesses causing morbidity, mortality and economic losses. NoV infections are self-limiting in healthy individuals but are associated with severe complica¬tions in immunocompromised individuals, the elderly and young children. In addition, frequently occurring new NoV genotypes and variants can cause large outbreaks and epidemics worldwide. Very little is known about NoV infections in most non-human hosts and the close genetic similarities between some animal and human NoVs leads to the realistic hypothesis that the virus might jump the species barrier triggering pandemic variants. Importantly, no therapy is currently available to treat or prevent NoV infections. The requirement for NoVs to attach to specific glycans to infect hosts’ tissues, and cells, has been well established but the underlying mechanisms remain to be elucidated. Going beyond the state-of-the-art, the overall aims of GlycoNoVi is training 9 researchers to address knowledge gaps on NoV glycan interactions and investigate the exciting possibility of developing synthetic glycans as antiviral strategies to treat NoV infection. These aims will be achieved bringing together 6 academic and 4 industrial leaders in glycoscience, glycovirology and NoV field and relying on a multidisciplinary and interconnected approach which is declinate in research-oriented WP1-5 and WP6-8 focused respectively on training, outreach and coordination.

Globally, NoV are associated with ≈20% of acute gastroenteritis cases, causing an estimated 685 million episodes and 210.000 deaths each year. Despite much research during the last 20 years, there are still no drugs available for the treatment of NoV infection and candidate vaccines approval is still far behind in that NoV is constantly expanding its genetic diversity. In short terms, GlycoNoVi scientific acquisitions will enable scientists to raise non specialist and consumer awareness on NoV infections also improving policies and decision-making (strategies to reduce contagious, prevent outbreak, reduce source of infection). A better understanding of which binding characteristics are crucial for NoV emergence will also help to improve NoVsurveillance and future vaccine policies. In the long term, GlycoNoVi will significantly accelerate the development of antiviral drugs or a vaccine candidate to treat NoV with an enormous societal impact in terms of avoidable mortality, especially in children by 2 years of age, hospitalized adults and less developed countries’ population.