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碳水化合物:影响神经的病原体的结合部位和潜在药物靶点。

Carbohydrates: Binding Sites and Potential Drug Targets for Neural-Affecting Pathogens.

机构信息

Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.

出版信息

Adv Neurobiol. 2023;29:449-477. doi: 10.1007/978-3-031-12390-0_15.

Abstract

A number of viruses that have caused wide spread concern e.g. Ebola, Zika, and SARS-CoV2 (severe acute respiratory syndrome coronavirus 2 also known as COVID 19) have at various times, become newsworthy as a result of being newly discovered, mutations enabling them to more efficiently infect humans or modern modes of transportation moving them to areas with naive, susceptible populations. As more is learned about the mechanisms whereby these pathogens enter human cells it has become increasingly evident that carbohydrates expressed on the surface of either target cells or the pathogens themselves are essential. Variability in carbohydrate structures as well as the presence of carbohydrate binding receptors (lectins) provides a plethora of potential binding interactions by which infection of cells can occur. Identification of specific lipid- or protein-associated carbohydrates essential for infection provides support for research being done to develop carbohydrate related inhibitors of those interactions. This chapter (1) discusses scenarios for how carbohydrates affect the ability of specific infectious agents to interact with neural cells, (2) gives examples of problems that may result from development of antibodies to carbohydrate antigens found on pathogens that are similar to epitopes expressed on mammalian cells, and (3) provides examples of approaches either in use or under consideration for translational uses of this information.

摘要

已经引起广泛关注的许多病毒,例如埃博拉病毒、寨卡病毒和严重急性呼吸综合征冠状病毒 2(也称为 COVID-19),由于新发现、使它们能够更有效地感染人类的突变,或现代交通工具将它们转移到天真易感人群的地区,在不同时间成为新闻焦点。随着人们对这些病原体进入人体细胞的机制的了解越来越多,越来越明显的是,无论是靶细胞表面还是病原体本身表达的碳水化合物都是必不可少的。碳水化合物结构的可变性以及碳水化合物结合受体(凝集素)的存在提供了大量潜在的结合相互作用,通过这些相互作用可以发生细胞感染。鉴定对感染至关重要的特定脂质或蛋白相关碳水化合物,为研究开发针对这些相互作用的碳水化合物相关抑制剂提供了支持。本章(1)讨论了碳水化合物如何影响特定传染性病原体与神经细胞相互作用的能力的情况,(2)给出了由于针对与哺乳动物细胞表达的表位相似的病原体上的碳水化合物抗原产生抗体而可能产生的问题的例子,以及(3)提供了正在使用或正在考虑用于转化用途的这种信息的方法的例子。

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