Glycyrrhizin inhibits influenza A virus uptake into the cell.

Glycyrrhizin inhibits influenza A virus uptake into the cell.
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DOI:
10.1016/j.antiviral.2009.04.012
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发表时间:
2009-08
期刊:
影响因子:
7.6
通讯作者:
Szolar OH
Szolar OH
中科院分区:
医学2区
文献类型:
--
作者:
Wolkerstorfer A;Kurz H;Bachhofner N;Szolar OH

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我们研究了甘草的主要活性成分甘草素(GL)保护细胞免受甲型流感病毒(IAV)感染的机制。我们发现,GL治疗导致IAV感染的人肺细胞数量明显减少,CCID50滴度降低90%。然而,抗病毒作用仅限于一个或两个病毒复制周期。对不同GL治疗方案的分析表明,GL的抗病毒作用仅限于病毒复制周期的早期阶段。GL对IAV颗粒的直接抑制作用可以排除,GL也不与病毒受体结合相互作用。GL的抗病毒作用在病毒感染后1 h通过治疗消除,而预处理和病毒吸附期间和之后的治疗导致细胞病变效应减少,细胞内和细胞上清液中的病毒RNA减少,病毒血凝滴度降低。详细的病毒摄取分析明确表明,在各种GL处理的细胞中,病毒摄取减少。这些观察结果得出结论,GL的抗病毒活性是通过与细胞膜的相互作用介导的,这最有可能导致内吞活性降低,从而降低病毒摄取。这些见解可能有助于设计结构相关的化合物,从而产生有效的抗流感疗法。
We investigated the mechanism by which glycyrrhizin (GL), the main active component of licorice roots, protects cells from infection with influenza A virus (IAV). We found that GL treatment leads to a clear reduction in the number of IAV-infected human lung cells as well as a reduction in the CCID50 titer by 90%. The antiviral effect, however, was limited to one or two virus replication cycles. Analysis of different GL treatment protocols suggested that the antiviral effect of GL was limited to an early step in the virus replication cycle. A direct inhibitory action of GL on IAV particles could be excluded and GL did not interact with virus receptor binding either. The antiviral effect of GL was abolished by treatment 1 h after virus infection, whereas pre-treatment and treatment during and after virus adsorption led to a reduction in the cytopathic effect, reduced viral RNA within the cells and in the cell supernatants, and reduced viral hemagglutination titers. Detailed virus uptake analyses unambiguously demonstrated reduced virus uptake in various GL-treated cells. These observations lead to the conclusion, that the antiviral activity of GL is mediated by an interaction with the cell membrane which most likely results in reduced endocytotic activity and hence reduced virus uptake. These insights might help in the design of structurally related compounds leading to potent anti-influenza therapeutics.
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