Human cytomegalovirus-inhibitory flavonoids: studies on antiviral activity and mechanism of action.
Human cytomegalovirus-inhibitory flavonoids: studies on antiviral activity and mechanism of action.
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DOI：
10.1016/j.antiviral.2005.08.002
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发表时间：
2005-12
影响因子：
7.6
通讯作者：
Huang ES
中科院分区：
文献类型：
--
作者：
Evers DL;Chao CF;Wang X;Zhang Z;Huong SM;Huang ES
我们报告抗人类巨细胞病毒的某些饮食黄酮类化合物和他们可能的生化作用机制。十分之九的评估类黄酮在浓度显着低于对生长期或稳定期宿主细胞产生细胞毒性的浓度下可以阻止HCMV复制。黄芩素是该系列中最有效的抑制剂（IC 50 = 0.4-1.2 μM），包括阳性对照更昔洛韦。以黄芩素和染料木黄酮为模型化合物，研究了该系列化合物的抗病毒作用机制。这两种黄酮类化合物显着降低HCMV早期和晚期蛋白的水平，以及病毒DNA的合成。黄芩素降低HCMV立即早期蛋白的水平接近背景水平，而染料木素没有。在细胞培养中，染料木黄酮的抗病毒作用是完全可逆的，而黄芩素则不然。预孵育浓缩的病毒股票与黄酮类化合物没有抑制HCMV复制，表明黄芩素不直接包裹病毒颗粒。黄芩素在功能上阻断表皮生长因子受体酪氨酸激酶活性和HCMV核转位，而染料木黄酮没有。在感染后24小时，用染料木黄酮处理的HCMV感染的细胞继续表达立即早期蛋白，并有效地磷酸化IE 1 -72。然而，HCMV对NF-κB的诱导和细胞周期调节蛋白水平的增加-与即刻早期蛋白功能相关的事件-是不存在的。这些数据表明，黄芩素的主要作用机制可能是阻断HCMV感染，而染料木素的主要作用机制可能是阻断HCMV立即早期蛋白功能。
We report antiviral activity against human cytomegalovirus for certain dietary flavonoids and their likely biochemical mechanisms of action. Nine out of ten evaluated flavonoids blocked HCMV replication at concentrations that were significantly lower than those producing cytotoxicity against growing or stationary phase host cells. Baicalein was the most potent inhibitor in this series (IC50 = 0.4–1.2 μM), including positive control ganciclovir. Baicalein and genistein were chosen as model compounds to study the antiviral mechanism(s) of action for this series. Both flavonoids significantly reduced the levels of HCMV early and late proteins, as well as viral DNA synthesis. Baicalein reduced the levels of HCMV immediate-early proteins to nearly background levels while genistein did not. The antiviral effects of genistein, but not baicalein, were fully reversible in cell culture. Pre-incubation of concentrated virus stocks with either flavonoid did not inhibit HCMV replication, suggesting that baicalein did not directly inactivate virus particles. Baicalein functionally blocked epidermal growth factor receptor tyrosine kinase activity and HCMV nuclear translocation, while genistein did not. At 24 h post infection HCMV-infected cells treated with genistein continued to express immediate-early proteins and efficiently phosphorylate IE1-72. However, HCMV induction of NF-κB and increases in the levels of cell cycle regulatory proteins—events that are associated with immediate-early protein functioning – were absent. The data suggested that the primary mechanism of action for baicalein may be to block HCMV infection at entry while the primary mechanism of action for genistein may be to block HCMV immediate-early protein functioning.
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影响因子：
7.6
作者：
Hippenmeyer, PJ;Dilworth, VM
通讯作者：
Dilworth, VM
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作者：
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5.4
作者：
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HUANG, ES
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