Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1.

Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1.
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DOI:
10.1016/j.antiviral.2011.08.017
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发表时间:
2011-11
期刊:
影响因子:
7.6
通讯作者:
Tiwari, Vaibhav
Tiwari, Vaibhav
中科院分区:
医学2区
文献类型:
--
作者:
Mishra, Yogendra Kumar;Adelung, Rainer;Roehl, Claudia;Shukla, Deepak;Spors, Frank;Tiwari, Vaibhav

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1型单纯疱疹病毒(HSV-1)进入靶细胞是由带正电的病毒包膜糖蛋白与带负电的细胞表面硫酸乙酰肝素(HS)之间的离子相互作用启动的。第一步涉及在细胞表面诱导富含HS的丝状伪足样结构,其在细胞进入期间促进病毒运输。针对HSV-1发病机制中的这一最初的第一步,我们产生了不同的氧化锌(ZnO)微纳米结构(MNS),其被多个纳米级尖峰覆盖,模仿细胞诱导的丝状伪足。预测这些MNS靶向病毒,以通过其纳米级尖峰上的部分带负电荷的氧空位竞争其与细胞HS的结合,从而影响病毒进入和随后的传播。我们的研究结果表明,部分带负电荷的氧化锌MNS有效地捕获病毒粒子通过一种新的病毒抑制机制,使他们无法进入人类角膜成纤维细胞-HSV-1感染的天然靶细胞。在紫外光照射下,ZnO纳米结构的抗HSV-1活性在产生额外的氧空位后显著增强。我们的研究结果提供了一个新的见解ZnO MNS作为有效的HSV-1抑制剂的意义和合理的开发作为一种新的局部药物预防HSV-1感染。
Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal fibroblasts-a natural target cell for HSV-1 infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after creating additional oxygen vacancies under UV-light illumination. Our results provide a novel insight into the significance of ZnO MNSs as the potent HSV-1 inhibitor and rationalize their development as a novel topical agent for the prevention of HSV-1 infection.
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