Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Marta Utratna, S. Deegan, L. Joshi
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引用次数: 2

Abstract

Pathogen adherence to a host cell is one of the first essential steps for establishing invasion, colonization and release of virulence factors such as toxins. Understanding the mechanisms used by pathogens and toxins to adhere and invade human cells could lead to the development of new strategies for preventing and controlling the spread of infectious diseases. This review focuses on carbohydrate-lectin interactions utilized by selected biothreat agents to bind and invade host cells. The principle of using anti-adhesion molecules, based on glycobiology research, has already been shown to be effective in the treatment of influenza. Therefore, translating the same principle to other biothreat agents that mediate invasion of a host cell through carbohydrate-lectin mechanisms is a very promising strategy. We investigate recent literature to highlight the latest developments in the field of glycobiology focused on inhibiting the initial steps of pathogen invasion, with examples for bacteria, toxin and virus interactions. The successful glycomimetics and glycoconjugates represent strategies for interruption of adhesion by single molecules and in multivalent systems against uropathogenic E. coli, several toxins (Shiga-like, cholera, botulinum) and well-known or emerging viruses (influenza, HIV, Ebola, and Zika). This review provides promising directions and prophylactic as well as therapeutic potential of anti-adhesive strategies against selected biothreat targets.
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糖生物学在生物威胁剂抗粘附方法中的应用
病原体粘附于宿主细胞是建立入侵、定植和释放毒力因子(如毒素)的首要步骤之一。了解病原体和毒素粘附和侵入人体细胞的机制可能会导致制定预防和控制传染病传播的新战略。本文综述了碳水化合物-凝集素相互作用的选择生物威胁剂利用结合和入侵宿主细胞。基于糖生物学研究,使用抗黏附分子的原理已被证明对治疗流感有效。因此,将相同的原理转化为通过碳水化合物-凝集素机制介导宿主细胞入侵的其他生物威胁剂是一种非常有前途的策略。我们研究了最近的文献,以突出糖生物学领域的最新发展,重点是抑制病原体入侵的初始步骤,并举例说明细菌、毒素和病毒的相互作用。成功的糖仿制品和糖缀合物代表了单分子和多价系统中针对尿路致病性大肠杆菌、几种毒素(志贺样、霍乱、肉毒杆菌)和已知或新出现的病毒(流感、艾滋病毒、埃博拉和寨卡病毒)的粘附中断策略。本文综述了针对特定生物威胁靶点的抗黏附策略的预防和治疗潜力。
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