NMR investigations into norovirus-receptor recognition

诺如病毒（NV）感染对人类健康的威胁日益严重。既没有抗病毒治疗，也没有任何疫苗。已知组织血型抗原（HBGAs）作为绝大多数NV的主要受体。为了提出任何治疗概念，从根本上需要更好地理解受体识别的分子基础，特别是逃避人类免疫应答和受体识别之间的相互作用。我们建议利用NMR实验表征不同株NV VLP（病毒样颗粒）与HBGA受体在原子分辨率下的结合。NV VLP/HBGA结合过程的热力学参数将从表面等离子体共振测量和等温滴定微量热法获得。小化合物库以及天然和合成糖库的STD NMR筛选将提供关于不同NV菌株与HBGA的结合要求的基本信息。同时，我们也希望能为设计特异性NV进入抑制剂提供依据，从而为开发抗诺如病毒感染的治疗方法铺平道路。

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.