Objective Norovirus infections affect more than 200 million people worldwide every year. Since these viruses are highly contagious and cause epidemic outbreaks norovirus infections constitute a massive economic burden. Currently there are neither vaccination strategies nor therapeutics to cure the infection. We have designed first prototype entry-inhibitors against norovirus infections employing a rational approach based on NMR binding studies with virus like particles (VLPs). In order to develop these prototype inhibitors into potent antivirals information is needed on the thermodynamics and kinetics of binding of entry-inhibitors to the viral coat protein VP1. Binding data will be related to binding topologies on the surface of VP1. We suggest protein NMR experiments with selectively 2H/15N/13C amino acid labeled VP1 to study the relative binding topologies of natural attachment factors and entry-inhibitors. Isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) will yield enthalpies and entropies of binding as well as kinetic data on the binding process. Thermodynamic data in combination with relative binding topologies will then deliver guides for the rational modification of the first generation inhibitors to obtain better affinities. The modified compounds will be subjected to the same set of experiments, and depending on the results the optimization process proceeds in an iterative manner until potent entry-inhibitors are identified. Since VP1 is expressed as a homodimer (P-dimer), potent inhibitor candidates will be linked to a polymeric backbone as described earlier in order to achieve better avidity. Finally, we hope to come up with a first rationally designed entry-inhibitor against norovirus infections. Fields of science natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesphysical sciencesthermodynamicsnatural sciencesmathematicspure mathematicstopologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2012-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITAET zu LUEBECK EU contribution € 161 968,80 Address RATZEBURGER ALLEE 160 23562 Lubeck Germany See on map Region Schleswig-Holstein Schleswig-Holstein Lübeck, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Margret Schwab (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data