Human norovirus (HuNoV), causative agent of acute gastroenteritis has no vaccine or anti-viral treatment. Gastroenteritis is the leading cause of hospitalisation in Pacific Island children in NZ. HuNoV infections predominate in the health care industry costing $50.5 million annually. The impediment to vaccine discovery is the inability to propagate HuNoV in the laboratory. This project will determine the role of HuNoV protein NS1-2 on cell transcription, signalling and immune-modulation. NZ1-2 is an ideal drug target as it contains segments of protein with inherently disordered regions (IDR). Viral IDR proteins are also multifunctional and are crucial for virus replication. Mammalian IDR proteins are also multifunctional and their dysfunction is linked to development of cardiovascular disease, diabetes, neurogenerative conditions, and cancers. The results from this project will not only identify anti-viral targets to block HuNoV infection, they will further our knowledge of IDR proteins and design of small molecule inhibitors to use as therapeutics.