Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro
Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro
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阿比朵尔对乳鼠和体外致命汉坦病毒感染的功效
DOI：
10.1038/aps.2009.53
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发表时间：
2009-07-01
影响因子：
8.2
通讯作者：
Yang, Zhan-qiu
中科院分区：
文献类型：
--
作者：
Deng, Hai-ying;Luo, Fan;Yang, Zhan-qiu
目的：阿比朵尔是一种免疫调节剂，首先在俄罗斯开发。在本研究中，我们报告了阿比朵尔对汉坦病毒（HTNV）的体外和体内抗病毒活性。方法：通过空斑形成试验测定阿比朵尔的体外抗病毒活性，范围为0.5至8μg/mL。为研究阿比朵尔在体内是否具有抗病毒作用，感染HTNV的哺乳期BALB/c小鼠在感染前24小时给予阿比朵尔5、10或20 mg.kg(-1).d(-1)，每天一次，持续10天。感染后第 12 天和第 28 天 (pi)，检测到组织病理学变化和病毒抗原。感染后第4、8、12和16天，测定阿比朵尔治疗动物的靶器官病毒载量和血清TNF-α水平。结果：发现在病毒感染前或病毒感染后体外添加阿比朵尔对HTNV具有强效抑制活性，50%抑制浓度（IC50）分别为0.9和1.2μg/mL。阿比朵尔对乳鼠的50%致死剂量(LD50)为78.42 mg.kg(-1).d(-1)。口服阿比多尔可增加生存率和平均死亡时间（MTD）。阿比朵尔治疗减少了组织病理学变化，降低了病毒载量和病毒抗原水平，并调节了血清TNF-α水平。结论：阿比朵尔能够在体内和体外引发针对HTNV的保护性抗病毒活性。
Aim: Arbidol is an immunomodulator that was first developed in Russia. In this study, we report the antiviral activity of arbidol against Hantaan virus (HTNV) in vitro and in vivo.Methods: The antiviral activity of arbidol in vitro was determined by plaque-forming assay, ranging from 0.5 to 8 mu g/mL. To investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice infected with HTNV were treated with arbidol at 24 h before infection with a 5, 10 or 20 mg.kg(-1).d(-1), once per day, for 10 days. On day 12 and 28 post infection (pi), histopathological changes and viral antigen were detected. On days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-alpha levels of arbidol-treated animals were determined.Results: Arbidol was found to have potent inhibitory activity against HTNV when added in vitro before or after viral infection, with a 50% inhibitory concentration (IC50) of 0.9 and 1.2 mu g/mL, respectively. The 50% lethal dose (LD50) of arbidol for suckling mice was 78.42 mg.kg(-1).d(-1). Oral administration of arbidol increased both survival rate and mean time to death (MTD). Treatment with arbidol reduced histopathological changes, decreased viral load and viral antigen levels, and modulated the level of serum TNF-alpha.Conclusion: Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.