Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki, 852-8521, Japan.
Arch Virol. 2011 Aug;156(8):1359-69. doi: 10.1007/s00705-011-0989-9. Epub 2011 Apr 9.
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.
甲型流感病毒（IAV）感染是一个重大的公共卫生威胁，导致发病率和死亡率显著增加。耐药病毒株的出现凸显了开发具有替代作用机制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化合物，具有广泛的生物活性。在本研究中，我们发现 PGG 具有抗流感病毒活性，并在体外研究了其可能的作用机制。在感染前预孵育病毒和用 PGG 处理感染细胞后，均可显著抑制病毒产量。PGG 处理可抑制流感病毒诱导的鸡红细胞凝集，表明 PGG 可通过与病毒血凝素相互作用抑制 IAV 感染。PGG 不影响病毒蛋白合成或病毒核蛋白（NP）的核转运，但可大大减少复制周期晚期 NP 蛋白在质膜上的积累。此外，PGG 可显著减少感染细胞中的病毒出芽和子代病毒释放。本研究首次揭示 PGG 可通过双重作用模式抑制 IAV 复制，并为其抗病毒作用的潜在机制提供了新的见解。
