Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
复制标题
黄酮类化合物对体外和新生小鼠肠道病毒 71 感染的抗病毒功效
DOI：
10.3390/v11070625
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发表时间：
2019-07-01
期刊：
影响因子：
4.7
通讯作者：
Su, Weiheng
中科院分区：
文献类型：
--
作者：
Dai, Wenwen;Bi, Jinpeng;Su, Weiheng
肠道病毒71型(EV71)感染已知会导致手足口病(HFMD)，这与神经系统并发症有关；然而，目前还没有有效的治疗这种感染的方法。黄酮类化合物是一大类天然存在的具有多种生物活性的化合物，几种黄酮类化合物在细胞培养中对EV71的抑制作用已经被研究，但到目前为止，还没有关于它们在动物模型中的作用的报道。在本研究中，我们在抑制细胞病变效应的基础上，证实了八个黄酮类化合物的体外抗EV71感染活性。此外，这些黄酮类化合物被发现可以减少病毒基因组RNA的复制和蛋白质的合成。我们进一步证明了这些黄酮类化合物对感染致死剂量EV71的新生小鼠的保护作用。芹菜素、木犀草素、山奈酚、芒柄花素和秋水仙素对EV71致死性攻击的保护率分别为88.89%、91.67%、88.89%、75%和66.67%。此外，异鼠李素在10 mg/kg剂量下对小鼠的存活保护作用最强，达100%。据我们所知，本研究首次评价了多种黄酮类化合物的体内抗EV71活性，从而确定了黄酮类化合物是潜在的抗EV71药物开发的先导化合物。
Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures; however, to date, there are no reported data on their effects in animal models. In this study, we confirmed the in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in newborn mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development.