Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus
Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus
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DOI：
10.1007/s00705-011-0989-9
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发表时间：
2011-08-01
影响因子：
2.7
通讯作者：
Kitazato, Kaio
中科院分区：
文献类型：
--
作者：
Liu, Ge;Xiong, Sheng;Kitazato, Kaio
甲型流感病毒（IAV）感染是导致显著发病率和死亡率的主要公共卫生威胁。耐药病毒株的出现凸显了开发具有替代作用模式的新型抗病毒药物的迫切需要。五没食子酰葡萄糖（PGG）是一种天然存在的多酚类化合物，具有广泛的生物活性。本研究发现PGG具有抗流感病毒活性，并对其可能的作用机制进行了体外研究。无论是感染前的病毒预孵育和感染细胞后暴露与PGG显着抑制病毒产量。PGG对流感病毒诱导的鸡红细胞凝集反应有抑制作用，提示PGG可能通过与病毒血凝素相互作用而抑制IAV感染。PGG不影响病毒蛋白质的合成和核转运，但在复制周期的后期大大减少了NP蛋白在质膜上的积累。此外，PGG显着减少病毒出芽和子代病毒从感染细胞的释放。这项研究首次揭示了PGG可以以双重作用模式抑制IAV复制，并为其抗病毒作用的潜在机制提供了新的见解。
Influenza A virus (IAV) infection is a major public health threat leading to significant morbidity and mortality. The emergence of drug-resistant virus strains highlights the urgent need to develop novel antiviral drugs with alternative modes of action. Pentagalloylglucose (PGG), a naturally occurring polyphenolic compound, possesses a broad spectrum of biological activities. In this study, we found that PGG has anti-influenza-virus activity, and investigated its possible mechanism(s) of action in vitro. Both pre-incubation of virus prior to infection and post-exposure of infected cells with PGG significantly inhibited virus yields. Influenza-virus-induced hemagglutination of chicken red blood cells was inhibited by PGG treatment, suggesting that PGG can inhibit IAV infection by interacting with the viral hemagglutinin. PGG did not affect viral protein synthesis or nuclear transport of viral nucleoprotein (NP) but greatly reduced plasma membrane accumulation of NP protein at the late stage of the replication cycle. Furthermore, PGG significantly reduced virus budding and progeny virus release from infected cells. This study revealed for the first time that PGG can inhibit IAV replication with a dual mode of action and offers new insights into its underlying mechanisms of antiviral action.