Multivalent Flexible Nanogels Exhibit Broad-Spectrum Antiviral Activity by Blocking Virus Entry
Multivalent Flexible Nanogels Exhibit Broad-Spectrum Antiviral Activity by Blocking Virus Entry
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DOI：
10.1021/acsnano.8b01616
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发表时间：
2018-07-01
期刊：
影响因子：
17.1
通讯作者：
Azad, Walid
中科院分区：
文献类型：
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作者：
Dey, Pradip;Bergmann, Tobias;Azad, Walid
病毒进入宿主细胞的过程是复杂的，涉及与不同细胞表面受体的稳定但短暂的多价相互作用。几种病毒的最初接触始于与细胞表面上的硫酸乙酰肝素（HS）蛋白聚糖的附着，这导致以病毒进入结束的级联事件。基于多价相互作用的抗病毒药物的开发，以屏蔽病毒颗粒并阻断与细胞受体的初始相互作用，引起了抗病毒研究的关注。在这里，我们设计了具有不同程度的灵活性的纳米凝胶的基础上树枝状聚甘油硫酸酯模仿细胞HS。所设计的纳米凝胶无毒、广谱，可以与病毒糖蛋白多价相互作用，屏蔽病毒表面，有效阻断感染。我们还可视化病毒纳米凝胶的相互作用，以及通过网格蛋白介导的内吞作用，使用共聚焦显微镜的细胞的纳米凝胶的摄取。由于许多人类病毒通过HS部分附着在细胞上，我们引入了我们的柔性纳米凝胶作为这些病毒的强大抑制剂。
The entry process of viruses into host cells is complex and involves stable but transient multivalent interactions with different cell surface receptors. The initial contact of several viruses begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface, which results in a cascade of events that end up with virus entry. The development of antiviral agents based on multivalent interactions to shield virus particles and block initial interactions with cellular receptors has attracted attention in antiviral research. Here, we designed nanogels with different degrees of flexibility based on dendritic polyglycerol sulfate to mimic cellular HS. The designed nanogels are nontoxic and broad-spectrum, can multivalently interact with viral glycoproteins, shield virus surfaces, and efficiently block infection. We also visualized virus-nanogel interactions as well as the uptake of nanogels by the cells through clathrin-mediated endocytosis using confocal microscopy. As many human viruses attach to the cells through HS moieties, we introduce our flexible nanogels as robust inhibitors for these viruses.