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与H1N1、H5N1及人流感相关的特定寡糖的构象和连接研究,用于开发第二代达菲。

Conformation and Linkage Studies of Specific Oligosaccharides Related to H1N1, H5N1, and Human Flu for Developing the Second Tamiflu.

作者信息

Yoo Eunsun

机构信息

College of Health Science, Honam University, Gwangju 506-714, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2014 Feb;22(2):93-9. doi: 10.4062/biomolther.2014.005.

Abstract

The interaction between viral HA (hemagglutinin) and oligosaccharide of the host plays an important role in the infection and transmission of avian and human flu viruses. Until now, this interaction has been classified by sialyl(α2-3) or sialyl(α2-6) linkage specificity of oligosaccharide moieties for avian or human virus, respectively. In the case of H5N1 and newly mutated flu viruses, classification based on the linkage type does not correlate with human infection and human-to-human transmission of these viruses. It is newly suggested that flu infection and transmission to humans require high affinity binding to the extended conformation with long length sialyl(α2-6)galactose containing oligosaccharides. On the other hand, the avian flu virus requires folded conformation with sialyl(α2-3) or short length sialyl(α2-6) containing trisaccharides. This suggests a potential future direction for the development of new species-specific antiviral drugs to prevent and treat pandemic flu.

摘要

病毒血凝素(HA)与宿主寡糖之间的相互作用在禽流感病毒和人流感病毒的感染与传播中起着重要作用。到目前为止,这种相互作用分别根据寡糖部分对禽流感病毒或人流感病毒的唾液酸(α2-3)或唾液酸(α2-6)连接特异性进行分类。就H5N1和新突变的流感病毒而言,基于连接类型的分类与这些病毒的人类感染及人际传播并无关联。最新研究表明,流感病毒感染人类并在人际间传播需要与含有长链唾液酸(α2-6)半乳糖的延伸构象具有高亲和力结合。另一方面,禽流感病毒需要与含有唾液酸(α2-3)或短链唾液酸(α2-6)的三糖折叠构象结合。这为开发预防和治疗大流行性流感的新型物种特异性抗病毒药物指明了潜在的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/373b/3975476/729802557aeb/BT22-2-0093f1.jpg

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