Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
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DOI：
10.1111/j.1462-5822.2007.00902.x
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发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Ludwig, Stephan
中科院分区：
文献类型：
--
作者：
Mazur, Igor;Wurzer, Walter J.;Ludwig, Stephan
流感仍然是世界范围内的主要瘟疫之一。新的大流行爆发的统计可能性突出了对新的和充足的抗病毒药物的迫切需要。我们和其他人已经表明，流感病毒滥用细胞IKK/NF-κ B信号通路进行有效复制，这表明该模块可能是抗病毒干预的合适靶点。在这里，我们研究了乙酰水杨酸（阿萨），也称为阿司匹林，一种广泛使用的药物，具有众所周知的抑制NF-κ B的能力。我们表明，该药物有效地阻止流感病毒复制在体外和体内的机制，涉及受损的表达的促凋亡因子，随后抑制半胱天冬酶的激活，以及阻断半胱天冬酶介导的病毒核糖核蛋白的核输出。由于ASA没有毒副作用或诱导耐药病毒变异的倾向，现有的水杨酸酯气溶胶药物可能适合作为抗流感药物。这是第一次证明特异性靶向细胞因子是抗流感病毒干预的合适方法。
Influenza is still one of the major plagues worldwide. The statistical likeliness of a new pandemic outbreak highlights the urgent need for new and amply available antiviral drugs. We and others have shown that influenza virus misuses the cellular IKK/NF-kappa B signalling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here we examined acetylsalicylic acid (ASA), also known as aspirin, a widely used drug with a well-known capacity to inhibit NF-kappa B. We show that the drug efficiently blocks influenza virus replication in vitro and in vivo in a mechanism involving impaired expression of proapoptotic factors, subsequent inhibition of caspase activation as well as block of caspase-mediated nuclear export of viral ribonucleoproteins. As ASA showed no toxic side-effects or the tendency to induce resistant virus variants, existing salicylate-based aerosolic drugs may be suitable as anti-influenza agents. This is the first demonstration that specific targeting of a cellular factor is a suitable approach for anti-influenza virus intervention.