NMR-Untersuchung von Norovirus-Rezeptoren

Norovirus (NV) infections are a growing threat to human health. Neither is an antiviral therapy available, nor is any vaccine in sight. It is known that histo blood group antigens (HBGAs) serve as primary receptors for the vast majority of NVs. In order to come up with any therapeutic concept, there is a fundamental need for a better understanding of the molecular basis of receptor recognition, and in particular of the interplay between escape from the human immune response and receptor recognition. We propose to characterize the binding of different strains of NV VLPs (virus like particles) to HBGA receptors at atomic resolution utilizing NMR experiments. Thermodynamic parameters of the NV VLP/HBGA binding process will be obtained from surface plasmon resonance measurements, and isothermal titration microcalorimetry. STD NMR screening of small compound libraries as well as of natural and synthetic saccharide libraries will deliver essential information on the binding requirements of different NV strains to HBGAs. At the same time we hope to provide a basis for the rational design of specific NV entry-inhibitor and thus to pave the way for the development of a therapy against Norovirus infections.