Intestinal organoids as models for the development of antivirals against human norovirus and rotavirus.

The project will investigate viral replication assays in gut organoids towards their use in exploring novel antiviral strategies to combat noro- and rotavirus infections. The major limitation to develop novel small molecule inhibitors for human noro- (HuNoV) and rotaviruses (HRV) is the lack of a robust in vitro or in vivo culture model. Gut organoids will be implemented to study infection and replication of multiple HuNoV and HRV strains. The effect of (i) previously described antivirals with in vitro and/or in vivo activity; (ii) novel inhibitors identified in a high throughput screening campaign (surrogate virus) of 150 000 molecules; (iii) other biologicals will be studied using this virus/gut organoid system. This will provide a unique opportunity to understand the interactions between these enteric pathogens and the gut epithelia and get further insight into details of their replication, such as viral entry and pathogenesis. Moreover, it will constitute a unique platform to assess the efficacy of inhibitors currently under development against previously uncultivable strains.