Development of antivirals against norovirus: linking the bench to the bedside
Ontwikkeling van nieuwe antivirale middelen tegen het norovirus: een verbinding tussen de laboratoriumtafel en het ziektebed
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.
|Keywords||Norovirus, transplantation, mycophenolic acid, interferon, nitazoxanide|
|Promotor||M.P. Peppelenbosch (Maikel) , Q. Pan (Qiuwei)|
|Publisher||Erasmus University Rotterdam|
|Note||For reasons of copyright there is a (partial) embargo for this dissertation|
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