The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo.
The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo.
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天然化合物高三尖杉酯碱在体外和体内具有广泛的抗病毒活性
DOI：
10.3390/v10110601
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发表时间：
2018-11-01
期刊：
影响因子：
--
通讯作者：
Wang XJ
中科院分区：
文献类型：
--
作者：
Dong HJ;Wang ZH;Meng W;Li CC;Hu YX;Zhou L;Wang XJ
为了补充传统的抗病毒药物，天然化合物通过宿主靶标发挥作用，并对耐药性表现出高屏障，越来越受到关注。高三尖杉酯碱（HHT）具有较强的抗病毒活性。在细胞培养物中，HHT分别在50、100和500 nM浓度下完全抑制水泡性口炎病毒（VSV）、纽卡斯尔病病毒（NDV）和猪流行性腹泻病毒（PEDV）的感染。用0.05或0.2 mg/kg剂量的HHT治疗显著降低了PEDV或NDV感染动物的病毒载量并缓解了严重症状。然而，HHT治疗适度抑制禽流感病毒（AIV）感染，表明其有效的抗病毒作用仅限于一些RNA病毒。在这项研究中，我们还观察到HHT积极抑制1型单纯疱疹病毒（HSV-1）的复制，50%抑制浓度（IC 50）为139 nM;用1000 nM的HHT处理导致病毒复制减少了三个数量级。HHT还能拮抗内源性和外源性真核起始因子4 E（p-eIF 4 E）的磷酸化水平，从而调节特异性信使RNA（mRNA）的选择性翻译。HHT为进一步开发广谱抗病毒药物提供了一个起点。
To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC50) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.
靶向NP mRNA的短发夹RNA抑制纽卡斯尔病毒的产生和其他病毒结构mRNA转录。
影响因子：
1.6
作者：
Yue H;Deng S;Yang FL;Li DF;Fu AJ;Yang F;Tang C
通讯作者：
Tang C