Biochemical and NMR Studies of Influenza HA2

描述（由申请人提供）：病毒包膜蛋白HA1和HA2在流感进入中起关键作用。HA2介导病毒和细胞膜的融合，从而允许流感遗传物质进入。指导假设是HA2的结构域可以作为体内存在的更大结构域的模型。本研究的长期目标是通过核磁共振光谱进行基本药物设计和高通量筛选，以设计破坏HA2功能并因此感染流感的新型抗病毒药物。具体目标是：(1)从已被充分表征的1968年H3菌株中生成并表征流感HA2结构，这些结构可用于生物物理表征和核磁共振光谱的药物发现；(2)从1918年导致迄今最致命的流感大流行的流感毒株中生成并表征流感HA2构建物，这些构建物可通过核磁共振光谱进行生物物理表征和药物发现；(3)最有前途的HA2结构体的结构和动力学性质将通过核磁共振光谱来确定。

DESCRIPTION (provided by applicant): The viral envelope proteins HA1 and HA2 play critical roles in influenza entry. HA2 mediates fusion of the viral and cellular membranes, thereby allowing entry of the influenza genetic material. The guiding hypothesis is that structural domains of HA2 can serve as models of the larger domain present in vivo. The long-term goal of this research is to perform rationale drug design and high throughput screening by NMR spectroscopy for novel antivirals that are designed to disrupt HA2 function and hence influenza infection. The specific aims are: (1) Generate and characterize influenza HA2 constructs, from the well characterized 1968 H3 strain, that are amenable for biophysical characterizations and drug discovery by NMR spectroscopy; (2) Generate and characterize influenza HA2 constructs, from the 1918 HI strain responsible for the most deadly flu pandemic to date, that are amenable for biophysical characterizations and drug discovery by NMR spectroscopy; (3) The structure and dynamic properties of the most promising HA2 constructs will be determined by NMR spectroscopy.