Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway.
Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway.
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岩藻依聚糖靶向病毒神经氨酸酶和细胞 EGFR 通路抑制甲型流感病毒感染
DOI：
10.1038/srep40760
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发表时间：
2017-01-17
影响因子：
4.6
通讯作者：
Yu G
中科院分区：
文献类型：
--
作者：
Wang W;Wu J;Zhang X;Hao C;Zhao X;Jiao G;Shan X;Tai W;Yu G
开发高效、低毒的抗甲型流感病毒（IAV）新药是预防流感暴发的关键。本研究旨在探讨岩藻多糖在体外和体内抗IAV的活性及其作用机制。结果表明，褐藻褐藻多糖KW能有效地阻断IAV的体外感染，且毒性低。KW具有广谱的抗IAV作用，诱导病毒耐药的倾向小，上级抗IAV药物金刚烷胺。KW能在病毒感染前灭活病毒颗粒，并在吸附后阻断某些阶段。KW可与病毒神经氨酸酶（NA）结合，抑制NA的活性，从而阻断IAV的释放。KW还可抑制IAV感染细胞中EGFR、PKCα、NF-κB和Akt的活化，并抑制IAV内吞和EGFR内化，提示KW还可抑制细胞EGFR通路。此外，KW的鼻内给药显著提高了IAV感染小鼠的存活率并降低了病毒滴度。因此，褐藻多糖硫酸酯KW有潜力开发成一种新型的滴鼻剂或喷雾剂，用于预防和治疗流感。
Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidanin vitroandin vivo. The results showed that a fucoidan KW derived from brown algaeKjellmaniella crassifoliaeffectively blocked IAV infectionin vitrowith low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future.