Inhibition of influenza virus replication by plant-derived isoquercetin
Inhibition of influenza virus replication by plant-derived isoquercetin
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DOI：
10.1016/j.antiviral.2010.08.016
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发表时间：
2010-11-01
影响因子：
7.6
通讯作者：
Chang, Kyeong-Ok
中科院分区：
文献类型：
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作者：
Kim, Yunjeong;Narayanan, Sanjeev;Chang, Kyeong-Ok
流感病毒感染人类和动物的呼吸系统，引起轻微到严重的疾病，可能导致死亡。虽然疫苗是可用的，但仍然非常需要流感抗病毒药物来减少疾病进展和病毒传播。目前有两类（M2通道阻滞剂和神经氨酸酶抑制剂）获fda批准的流感抗病毒药物可用，但人们非常担心病毒耐药性的出现。因此，及时开发针对流感病毒的新型抗病毒药物至关重要。植物源性多酚已被研究用于抗氧化活性，抗癌，心脏和神经保护作用。最近，一些多酚，如白藜芦醇和表没食子儿茶素没食子酸酯，在体外和/或体内显示出显著的抗流感活性。因此，我们研究了所选择的多酚对甲型和乙型流感病毒的抗病毒活性。在我们测试的多酚中，异槲皮素以最低的有效浓度抑制甲型和乙型流感病毒的复制。在异槲皮素和金刚烷胺的双重处理下，观察到协同效应对体外病毒复制的减少。在异槲皮素存在的情况下，病毒的连续传代没有导致耐药病毒的出现，在金刚烷胺或奥司他韦治疗中加入异槲皮素抑制了金刚烷胺或奥司他韦耐药病毒的出现。在流感病毒感染小鼠模型中，对接种人甲型流感病毒的小鼠腹腔注射异槲皮素可显著降低病毒滴度和肺部病理改变。我们的研究结果表明，异槲皮素可能有潜力成为一种治疗流感病毒感染的药物，并在与现有药物联合治疗时抑制耐药性。(C) 2010 Elsevier B.V.版权所有
Influenza virus infects the respiratory system of human and animals causing mild to severe illness which could lead to death. Although vaccines are available, there is still a great need for influenza antiviral drugs to reduce disease progression and virus transmission. Currently two classes (M2 channel blockers and neuraminidase inhibitors) of FDA-approved influenza antiviral drugs are available, but there are great concerns of emergence of viral resistance. Therefore, timely development of new antiviral drugs against influenza viruses is crucial. Plant-derived polyphenols have been studied for antioxidant activity, anti-carcinogenic, and cardio- and neuroprotective actions. Recently, some polyphenols, such as resveratrol and epigallocatechin gallate, showed significant anti-influenza activity in vitro and/or in vivo. Therefore we investigated selected polyphenols for their antiviral activity against influenza A and B viruses. Among the polyphenols we tested, isoquercetin inhibited the replication of both influenza A and B viruses at the lowest effective concentration. In a double treatment of isoquercetin and amantadine, synergistic effects were observed on the reduction of viral replication in vitro. The serial passages of virus in the presence of isoquercetin did not lead to the emergence of resistant virus, and the addition of isoquercetin to amantadine or oseltamivir treatment suppressed the emergence of amantadine- or oseltamivir-resistant virus. In a mouse model of influenza virus infection, isoquercetin administered intraperitoneally to mice inoculated with human influenza A virus significantly decreased the virus titers and pathological changes in the lung. Our results suggest that isoquercetin may have the potential to be developed as a therapeutic agent for the treatment of influenza virus infection and for the suppression of resistance in combination therapy with existing drugs. (C) 2010 Elsevier B.V. All rights reserved.