Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment,Biochemistry

当前位置： X-MOL 学术 › Biochemistry › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment
Biochemistry ( IF 2.9 ) Pub Date : 2020-10-23 , DOI: 10.1021/acs.biochem.0c00732
M. Fernando Bravo _{1,

2,

3} , Manuel A. Lema _{1,

4} , Mateusz Marianski _{2,

3,

5} , Adam B. Braunschweig _{1,

2,

3,

5}

Affiliation

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.

中文翻译：

灵活的合成碳水化合物受体作为病毒附着的抑制剂。

糖与受体的相互作用通常参与病毒与宿主细胞的对接，而这种对接是病毒生命周期中感染和复制之前生命周期中必不可少的步骤。尽管涉及对接的聚糖的保守结构，它们仍然被认为是“不可药用的”，这意味着这些聚糖超出了常规药理策略的范围。合成碳水化合物受体（SCR）（与碳水化合物结合的小分子）发展的最新进展可能使碳水化合物-受体相互作用带入可治疗靶标的范围。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的进化，以及最近的结果证明了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。显示了将天然聚糖结合蛋白的特质（包括柔韧性，协同性和多价）纳入SCR设计以实现非糖苷特异性的好处。这些关于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的严重威胁的新战略，包膜病毒是糖基化程度很高的类病毒，是某些最紧迫和不可治愈的疾病的诱因，包括艾滋病毒，登革热，寨卡病毒，流感和SARS-CoV-2。

更新日期：2020-10-23

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11