Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment
Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment
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DOI：
10.1021/acs.biochem.0c00732
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发表时间：
2021-04-06
期刊：
影响因子：
2.9
通讯作者：
Braunschweig, Adam B.
中科院分区：
文献类型：
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作者：
Bravo, M. Fernando;Lema, Manuel A.;Braunschweig, Adam B.
碳水化合物-受体相互作用通常参与病毒与宿主细胞的对接，并且这种对接是病毒生命周期中感染和最终复制之前的必要步骤。尽管参与对接的聚糖的保守结构，但它们仍然被认为是“不可用药的”，这意味着这些聚糖超出了常规药理学策略的范围。合成碳水化合物受体（SCRs），结合碳水化合物的小分子的发展的最新进展，可以使碳水化合物-受体相互作用的范围内的药物靶点。在这里，我们讨论了碳水化合物-受体相互作用在病毒感染中的作用，SCR的演变，以及最近的结果表明它们在体外预防病毒感染的能力。讨论了基于硼酸酯形成、金属螯合和非共价相互作用的常见SCR设计策略。将天然聚糖结合蛋白质的特异性，包括灵活性，协同性和多价性纳入SCR设计，以实现nonglucosidic特异性的好处。这些对SCR设计和结合的研究可能会导致减轻包膜病毒对人类健康构成的严重威胁的新策略，包膜病毒是高度糖基化的类病毒，是一些最紧迫和不可治愈的疾病的原因，包括HIV，登革热，寨卡，流感和SARS-CoV-2。
Carbohydrate-receptor interactions are often involved in the docking of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered "undruggable", meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs), small molecules that bind carbohydrates, could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of SCRs, and recent results demonstrating their ability to prevent viral infections in vitro. Common SCR design strategies based on boronic ester formation, metal chelation, and noncovalent interactions are discussed. The benefits of incorporating the idiosyncrasies of natural glycan-binding proteins-including flexibility, cooperativity, and multivalency-into SCR design to achieve nonglucosidic specificity are shown. These studies into SCR design and binding could lead to new strategies for mitigating the grave threat to human health posed by enveloped viruses, which are heavily glycosylated viroids that are the cause of some of the most pressing and untreatable diseases, including HIV, Dengue, Zika, influenza, and SARS-CoV-2.