Pediatric Infectious Diseases Unit, University Children's Hospital Mannheim, University of Heidelberg, Heidelberg, Germany.
Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg, Germany.
Mol Nutr Food Res. 2018 Mar;62(6):e1700679. doi: 10.1002/mnfr.201700679. Epub 2018 Mar 1.
Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that are highly abundant in human breast milk. These glycans are investigated in the context of exhibiting multiple functions in infant growth and development. They seem to provide protection against infectious diseases, including a number of poorly manageable viral infections. Although the potential mechanism of the HMO antiviral protection is rather broad, much of the current experimental work has focused on studying of HMO antiadhesive properties. HMOs may mimic structures of viral receptors and block adherence to target cells, thus preventing infection. Still, the potential of HMOs as a source for new antiviral drugs is relatively unexploited. This can be partly attributed to the extreme complexity of the virus-carbohydrate interactions and technical difficulties in HMO isolation, characterization, and manufacturing procedures. Fortunately, we are currently entering a period of major technological advances that have enabled deeper insights into carbohydrate mediated viral entry, rational selection of HMOs as anti-entry inhibitors, and even evaluation of individual synthetic HMO structures. Here, we provide an up-to-date review on glycan binding studies for rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses. We also discuss the preventive and therapeutic potential of HMOs as anti-entry inhibitors and address challenges on the route from fundamental studies to clinical trials.
人乳寡糖（HMOs）是大量存在于人乳中的高度丰富的非共轭碳水化合物。这些糖在婴儿生长和发育中表现出多种功能的背景下进行研究。它们似乎提供了针对传染病的保护，包括许多难以控制的病毒性感染。尽管 HMO 的抗病毒保护的潜在机制相当广泛，但目前的大部分实验工作都集中在研究 HMO 的抗黏附特性上。HMO 可以模拟病毒受体的结构，阻止与靶细胞的黏附，从而防止感染。尽管如此，HMO 作为新型抗病毒药物的潜在来源尚未得到充分利用。这在一定程度上归因于病毒-碳水化合物相互作用的极端复杂性以及 HMO 分离、表征和制造过程中的技术困难。幸运的是，我们目前正进入一个重大技术进步的时期，这使得我们能够更深入地了解碳水化合物介导的病毒进入、作为抗进入抑制剂的 HMO 的合理选择，甚至评估单个合成 HMO 结构。在这里，我们提供了关于轮状病毒、诺如病毒、流感病毒和人类免疫缺陷病毒的聚糖结合研究的最新综述。我们还讨论了 HMO 作为抗进入抑制剂的预防和治疗潜力，并讨论了从基础研究到临床试验的途径上的挑战。
