Acta Pharmacologica Sinica (2009) 30: 1015-1024; doi: 10.1038/aps.2009.53; published online 8 June 2009

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

 

Hai-ying DENG1, 2, Fan LUO1, Li-qiao SHI1, Qiong ZHONG1, Ying-juan LIU1, Zhan-qiu YANG1,*

 

1State Key Laboratory of Virology, Institute of Medical Virology, School of Medicine, Wuhan University, Wuhan 430071, China; 2Medical School of Wuhan University of Science and Technology, Wuhan 430065, China

 

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 μg/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-α 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 μg/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-α. 

Conclusion: Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.

 

Keywords: antiviral activity; arbidol; Hantaan virus; suckling mice; in vitro; in vivo

 

This work was supported by a grant from the National Natural Science Foundation of China (NSFC project No 30873104).

We thank Dr Rhea-Beth MARKOWITZ and Dr Pamela Wall STEEN from the Medical College of Georgia, Augusta , Georgia , USA for critical reading of the manuscript.

 

* To whom correspondence should be addressed.
E-mail zqyang@whu.edu.cn
Received 2009-02-20     Accepted 2009-03-31

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