Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro.
OBJECTIVE
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 microg/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 (IC(50)) of 0.9 and 1.2 microg/mL, respectively. The 50% lethal dose (LD(50)) 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.


CONCLUSIONS
Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.Acta Pharmacologica Sinica (2009) 30: 1015-1024; doi: 10.1038/aps.2009.53; published online 8 June 2009.
Deng
Hai-Ying
HY
State Key Laboratory of Virology, Institute of Medical Virology, School of Medicine, Wuhan University, Wuhan 430071, China.
Luo
Fan
F
Shi
Li-Qiao
LQ
Zhong
Qiong
Q
Liu
Ying-Juan
YJ
Yang
Zhan-Qiu
ZQ
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000821:virology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology / Q000821:virology; D002460:Cell Line; D005260:Female; D018063:Hantaan virus / Q000187:drug effects*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology / Q000821:virology; D007928:Lethal Dose 50; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010919:Placebos; D011247:Pregnancy; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D013440:Sulfides
D000998:Antiviral Agents; D007155:Immunologic Factors; D007211:Indoles; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; C086979:umifenovir; D013440:Sulfides