Development of new antimicrobials: Rational design of polyomavirus and mycobacterial inhibitors

Promovendus/a: Stijn Lenders

Promotor(en): Prof. dr. Peter Verwilst, Prof. dr. Arthur Van Aerschot, Prof. dr. Sergei Strelkov

Within this thesis, we aimed to lay the groundworks for future treatments of two different endemic infections. In the first part, we sought a way to make the bacteria responsible for Tbc more susceptible to both the current line of drugs and the hosts own immune system. To do so, we targeted the biosynthesis of a certain defence molecule that the bacteria produce. The compounds synthesized for this project led to a better understanding of this pathway, and form an excellent basis for further research. In the second part, we looked for a way to stop the viral replication of the BKV polyomavirus. To do this, we attempted to prevent the virus from fully forming through the use of capsid assembly inhibitors. A fragment based screening found several fragments binding at the same place where the capsid is held together. We successfully expanded these fragments, and proved that they were able to prevent the proper assembly of the viral particle. Further research is still required to prove there effectiveness in a cell, after which they will be the first proof of concept molecules.