An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses
An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses
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DOI：
10.1016/j.immuni.2017.03.018
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发表时间：
2017-04-18
期刊：
影响因子：
32.4
通讯作者：
Jacob, Joshy
中科院分区：
文献类型：
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作者：
Holthausen, David J.;Lee, Song Hee;Jacob, Joshy
尽管疫苗可以预防甲型流感病毒，但由于没有足够的时间生产疫苗，抗病毒治疗成为大流行期间的第一道防线。目前的抗病毒药物容易产生耐药性，因此开发新的抗病毒药物至关重要。我们研究了来自南印度青蛙皮肤的宿主防御肽，并证明其中一种我们命名为“乌鲁木齐”的肽对携带H1血凝素的人类甲型流感病毒具有抗病毒作用。该肽特异性靶向H1血凝素的保守柄区，对耐药H1流感病毒有效。利用电子显微镜，我们发现这种肽在物理上破坏了流感病毒粒子。它还能保护幼鼠免受致命的流感感染。乌鲁木齐代表了一种独特的抗流感病毒杀菌剂，它专门针对血凝素柄区，类似于通用流感疫苗诱导的抗体靶向。因此，在流感爆发期间，乌鲁木齐有可能为一线抗病毒治疗做出贡献。
Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses. Using electron microscopy, we showed that this peptide physically destroyed influenza virions. It also protected naive mice from lethal influenza infection. Urumin represents a unique class of anti-influenza virucide that specifically targets the hemagglutinin stalk region, similar to targeting of antibodies induced by universal influenza vaccines. Urumin therefore has the potential to contribute to first-line anti-viral treatments during influenza outbreaks.