Punicalagin is a neuraminidase inhibitor of influenza viruses
Punicalagin is a neuraminidase inhibitor of influenza viruses
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DOI：
10.1002/jmv.26449
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发表时间：
2020-09-29
影响因子：
12.7
通讯作者：
Cui, Qinghua
中科院分区：
文献类型：
--
作者：
Li, Ping;Du, Ruikun;Cui, Qinghua
甲型流感病毒（Influenza A virus，IAV）每年在全世界范围内造成严重的发病率和死亡率。然而，临床上可用于抗IAV感染的药物数量有限。此外，抗药性菌株的出现可能使这些药物无效。因此，存在开发新的抗流感剂的未满足的医学需求。在这项研究中，我们表明，安石榴苷从植物中具有较强的抗流感病毒的活性，在组织培养的低微摩尔IC（50）值。使用电池的生物测定，如单循环复制试验，神经氨酸酶（NA）抑制试验，和病毒产量减少试验，我们证明了安石榴苷的主要作用机制（MOA）是NA介导的病毒释放。此外，安石榴苷可以抑制不同的甲型和B型流感病毒株的复制，包括奥司他韦耐药病毒（NA/H274 Y），表明安石榴苷是一种广谱抗IAV和IBV的抗病毒药物。此外，尽管安石榴苷像奥司他韦一样靶向NA，但它具有不同的MOA。这些结果表明，安石榴苷是一种流感NA抑制剂，可进一步开发为一种新型抗流感病毒药物。
Influenza A virus (IAV) causes great morbidity and mortality worldwide every year. However, there are only a limited number of drugs clinically available against IAV infection. Further, emergence of drug-resistant strains can render those drugs ineffective. Thus there is an unmet medical need to develop new anti-influenza agents. In this study, we show that punicalagin from plants possesses strong anti-influenza activity with a low micromolar IC(50)value in tissue culture. Using a battery of bioassays such as single-cycle replication assay, neuraminidase (NA) inhibition assay, and virus yield reduction assay, we demonstrate that the primary mechanism of action (MOA) of punicalagin is the NA-mediated viral release. Moreover, punicalagin can inhibit replication of different strains of influenza A and B viruses, including oseltamivir-resistant virus (NA/H274Y), indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV. Further, although punicalagin targets NA like oseltamivir, it has a different MOA. These results suggest that punicalagin is an influenza NA inhibitor that may be further developed as a novel antiviral against influenza viruses.