Mosquito-borne viruses have rapidly spread around the world, causing millions of clinically apparent infections with various symptoms from rashes and high fever to joint pain that can persist for years. The most common mosquito-borne virus is dengue virus, which causes an estimated 390 million infections each year. To date, there is no specific antiviral compound available to treat these viral diseases. Hence, there is a strong need for the identification and development of new treatment options towards these viruses. In this thesis, we investigated the antiviral potential of tomatidine, a natural compound found in the unripe green tomatoes, towards the mosquito-borne viruses dengue virus, zika virus, west nile virus and chikungunya virus as well as the underlying mode of action. Our work shows that tomatidine is able to reduce the infection of dengue and chikungunya virus in different human cell lines. Moreover, we found a significant but less potent antiviral activity of tomatidine towards zika virus but not towards west nile virus. Regarding the mode of action by which tomatidine exerts its antiviral activity, we found that tomatidine inhibits viral infection by interfering with the production of viral RNA and/or viral proteins which are required for the formation of new virus particles. The exact mechanism by which tomatidine exerts its antiviral activity still remains to be elucidated. Extensive pre-clinical and pharmacokinetic studies are still needed to further evaluate the potential of tomatidine as an antiviral compound in the future.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||31-mrt-2021|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2021|