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ESR-11 Characterisation of novel enterovirus inhibitors (KU Leuven)

Project description
The genus Enterovirus of the picornavirus family contains many important human and animal pathogens, such as poliovirus, coxsackievirus (CV), enterovirus 71 (EV71), and rhinovirus. Recently, a number of novel enterovirus inhibitors were discovered in our laboratory. The ESR will study the particular characteristics and unravel the molecular mechanism of action (MoA) of these inhibitors. The target of the compounds will be identified by selection and characterization of drug-resistant variants (e.g. subgenomic replicon analysis, resistance culturing, reverse genetics). The MoA of compounds targeting viral enzymes will be investigated in more detail by biochemical techniques (e.g. interaction analysis, enzymatic inhibition assays). Structure-based optimization of promising classes of molecules will be performed in close collaboration with structural biologists and medicinal chemists. The efficacy of the most potent molecules will be assessed in CVB3 and EV71 infection models in mice with emphasis on monitoring in vivo resistance development and quasispecies evolution under drug pressure.

The Network
This PhD position is part of the European training network ANTIVIRALS (www.antivirals-etn.eu). The candidate will benefit from the ANTIVIRALS network, which includes regular (scientific) network meetings and training in research methodology and complementary skills. This research project offers unique opportunities for establishing a broad and international scientific network with partners from the academic and industrial sector. The research project is performed in close collaboration with and partly at the premises of other institutions of the ANTIVIRALS network.

Host institute
The KU Leuven is a member of the League of European Research Universities (LERU) that share the values of high-quality teaching within an environment of internationally competitive research. The team of Prof. Johan Neyts (within the Rega Institute) is part of the department of Microbiology and Immunology at the KU Leuven (www.rega.kuleuven.be/cmt/jn). The focus of the lab is on the development of novel antiviral strategies. Examples of our activity include the discovery of a. Alisporivir (DEB025) currently in phase III studies at Novartis and Tegobuvir (7 phase 2 studies at Gilead Sciences) for the treatment of infections with HCV; b. potent and pan-serotype inhibitors of dengue virus replication, now being further developed in a joint effort with Janssen Pharmaceutica (Johnson & Johnson) c. highly potent and broad-spectrum inhibitors of rhino/enterovirus licensed to and being further developed by Novartis.

The Department of Microbiology and Immunology/Rega Institute for Medical Research currently hosts 69 PhD students. Prof. Neyts’ laboratory of Virology currently hosts 9 PhD students who carry out their research projects in the Institute’s laboratories and are registered in doctoral training programmes at the University of Leuven. These doctoral schools provide additional training courses to the PhD students with a focus on Virology themes as well as on broader themes which could be an asset to their future careers (e.g. communicative skills, presentation techniques, academic writing, etc.). The KU Leuven provides a multidisciplinary research environment and houses state-of-the art facilities for proteomics, genomics and advanced microscopy. The Neyts-lab is fully equipped for molecular virological, biochemical and antiviral studies (including two semi-automatic robotic facilities for antiviral drug screening).

Position filled