In Vitro Evaluation of Synergistic Inhibitory Effects of Neuraminidase Inhibitors and Methylglyoxal Against Influenza Virus Infection
In Vitro Evaluation of Synergistic Inhibitory Effects of Neuraminidase Inhibitors and Methylglyoxal Against Influenza Virus Infection
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DOI：
10.1016/j.arcmed.2014.12.002
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发表时间：
2015-01-01
影响因子：
7.7
通讯作者：
Kobayashi, Nobuyuki
中科院分区：
文献类型：
--
作者：
Charyasriwong, Siriwan;Watanabe, Ken;Kobayashi, Nobuyuki
背景和目标。流感病毒感染是全世界严重的公共卫生问题，导致相当大的死亡率和发病率。此外，对抗流感病毒剂的抗性的出现强调了开发新的抗流感病毒剂和新的治疗策略的需要。最近，我们发现了麦卢卡蜂蜜的抗流感病毒活性。因此，我们假设，甲基乙二醛（MGO），麦卢卡蜂蜜的关键成分，可能赋予抗流感病毒活性。本研究的目的是评估MGO的抗流感病毒活性及其与神经氨酸酶（NA）底物联合治疗的潜力。MDCK细胞用于评估抗流感病毒活性。为了评价MOO的机制，进行了空斑抑制试验。MOO和病毒NA抑制剂的协同作用进行了测试。MGO抑制流感病毒A/WSN/33复制的50%抑制浓度= 240 +/- 190 μ M; 50%细胞毒性浓度= 1.4 +/- 0.4 mM;选择指数（SI）= 5.8，这与其杀病毒作用有关。此外，我们发现MOO对各种流感病毒株显示出有希望的活性。通过NA抑制剂在其单次使用的1/100时SI的显著增加观察到协同效应。MOO和奥司他韦对奥司他韦耐药病毒也有协同作用。我们的研究结果表明，MGO对流感病毒具有有效的抑制活性，并且还增强了NA抑制剂的效果。因此，MGO和NA抑制剂的联合给药应考虑用于治疗流感病毒感染。(C)2015年IMSS。爱思唯尔公司出版
Background and Aims. Influenza virus infections are serious public health concerns worldwide that cause considerable mortality and morbidity. Moreover, the emergence of resistance to anti-influenza viral agents underscores the need to develop new anti-influenza viral agents and novel treatment strategies. Recently, we identified anti-influenza viral activity of manuka honey. Therefore, we hypothesized that methylglyoxal (MGO), a key component of manuka honey, may impart anti-influenza viral activity. The aim of this study was to evaluate the anti-influenza viral activity of MGO and its potential in combination treatments with neuraminidase (NA) inhibitors.Methods. MDCK cells were used to evaluate anti-influenza viral activity. To evaluate the mechanism of MOO, plaque inhibition assays were performed. The synergistic effects of MOO and viral NA inhibitors were tested.Results. MGO inhibited influenza virus A/WSN/33 replication 50% inhibitory concentration = 240 +/- 190 mu M; 50% cytotoxic concentration = 1.4 +/- 0.4 mM; selective index (SI) = 5.8, which is related to its virucidal effects. Moreover, we found that MOO showed promising activity against various influenza strains. A synergistic effect was observed by a marked increase in SI of NA inhibitors at similar to 1/100th of their single usage. A synergistic effect of MOO and oseltamivir was also observed against oseltamivir-resistant virus.Conclusions. Our results showed that MGO has potent inhibitory activity against influenza viruses and also enhanced the effect of NA inhibitors. Thus, the co-administration of MGO and NA inhibitors should be considered for treatment of influenza virus infections. (C) 2015 IMSS. Published by Elsevier Inc.