Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

被引:40
作者
Deng, Hai-ying [1 ,2 ]
Luo, Fan [1 ]
Shi, Li-qiao [1 ]
Zhong, Qiong [1 ]
Liu, Ying-juan [1 ]
Yang, Zhan-qiu [1 ]
机构
[1] Wuhan Univ, Sch Med, Inst Med Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
[2] Wuhan Univ Sci & Technol, Sch Med, Wuhan 430065, Peoples R China
基金
中国国家自然科学基金;
关键词
antiviral activity; arbidol; Hantaan virus; suckling mice; in vitro; in vivo; HEMORRHAGIC-FEVER; RENAL SYNDROME; INTRAVENOUS RIBAVIRIN; HANTAVIRUS INFECTION; TNF-ALPHA; INTERFERON; THERAPY; PATHWAY; AGENTS; RATS;
D O I
10.1038/aps.2009.53
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
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.
引用
收藏
页码:1015 / 1024
页数:10
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