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。目前还没有可用的抗病毒疗法，也没有任何疫苗。众所周知，组织血型抗原 (HBGA) 是绝大多数 NV 的主要受体。为了提出任何治疗概念，根本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反应和受体识别之间的相互作用。我们建议利用 NMR 实验以原子分辨率表征不同毒株 NV VLP（病毒样颗粒）与 HBGA 受体的结合。 NV VLP/HBGA 结合过程的热力学参数将从表面等离子共振测量和等温滴定微量热法获得。对小型化合物库以及天然和合成糖库进行 STD NMR 筛选将提供有关不同 NV 菌株与 HBGA 结合要求的重要信息。同时我们希望为特异性NV进入抑制剂的合理设计提供依据，从而为诺如病毒感染治疗的开发铺平道路。

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.