Even though norovirus gastroenteritis is normally self-limiting among immunocompetent individuals, it causes severe complications and fatal outcomes in immunocompromised patients. Hence novel and specific antiviral treatments are urgently needed. In this thesis, I aimed to adequately assess the burden of norovirus infection in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients, and to further explore the potency and mechanism­of-action of several chemicals in this specific setting. I found that the burden of norovirus infection in transplant recipients was more severe than was expected, thus requiring specific treatment. Mycophenolic acid exerted potent anti-norovirus activity through depletion of guanosine pool. Interferons induced strong anti­norovirus ISGs including IRF-1, RIG-I and MDAS to combat norovirus replication. Nitazoxanide inhibited human norovirus through activation of host innate immunity. These information bears important implication for developing antivirals against norovirus gastroenteritis.

Additional Metadata
Keywords Norovirus, transplantation, mycophenolic acid, interferon, nitazoxanide
Promotor M.P. Peppelenbosch (Maikel) , Q. Pan (Qiuwei)
Publisher Erasmus University Rotterdam
ISBN 978-94-6375-096-7
Persistent URL hdl.handle.net/1765/110021
Note For reasons of copyright there is a (partial) embargo for this dissertation
Citation
Dang, W. (2018, September 12). Development of antivirals against norovirus: linking the bench to the bedside. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/110021