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. 2012 Aug;7(8):801-818.
doi: 10.2217/fvl.12.71.

Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB/c mice

Yohichi Kumaki  1 , John D Morrey, Dale L Barnard
Affiliations

Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB/c mice

Yohichi Kumaki et al. Future Virol. 2012 Aug.

Abstract

Statins are used to control elevated cholesterol or hypercholesterolemia, but have previously been reported to have antiviral properties. AIMS: To show efficacy of statins in various influenza virus mouse models. MATERIALS & METHODS: BALB/c mice were treated intraperitoneally or orally with several types of statins (simvastatin, lovastatin, mevastatin, pitavastatin, atorvastatin or rosuvastatin) at various concentrations before or after infection with either influenza A/Duck/ MN/1525/81 H5N1 virus, influenza A/Vietnam/1203/2004 H5N1 virus, influenza A/ Victoria/3/75 H3N2 virus, influenza A/NWS/33 H1N1 virus or influenza A/CA/04/09 H1N1pdm09 virus. RESULTS: The statins administered intraperitoneally or orally at any dose did not significantly enhance the total survivors relative to untreated controls. In addition, infected mice receiving any concentration of statin were not protected against weight loss due to the infection. None of the statins significantly increased the mean day of death relative to mice in the placebo treatment group. Furthermore, the statins had relatively few ameliorative effects on lung pathology or lung weights at day 3 and 6 after virus exposure, although mice treated with simvastatin did have improved lung function as measured by arterial saturated oxygen levels in one experiment. CONCLUSION: Statins showed relatively little efficacy in any mouse model used by any parameter tested.

Keywords: BALB/c mouse; anti-inflammatory; atorvastatin; influenza virus; lovastatin; mevastatin; pitavastatin; rosuvastatin; simvastatin; statin.

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Conflict of interest statement

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1
Structures of various statins.
Figure 2
Figure 2
Effect of intraperitoneally administered simvastatin treatment on the survival of BALB/c mice infected with influenza A/NWS/33 H1N1 virus. ***p < 0.001. b.i.d.: Two times a day; CMC: Carboxymethyl cellulose; q.d.: Once daily.
Figure 3
Figure 3
Effect of intraperitoneal administered simvastatin treatment on the survival of BALB/c mice infected with influenza A/Victoria/3/75 H3N2 virus. **p = 0.005. b.i.d.: Two times a day; CMC: Carboxymethyl cellulose.
Figure 4
Figure 4
Effect of intraperitoneal administered simvastatin treatment on the survival of BALB/c mice infected with influenza A/Duck/MN/1525/81 H5N1 virus. ***p < 0.001. b.i.d.: Two times a day; CMC: Carboxymethyl cellulose; PSS: Physiologically sterile saline.
Figure 5
Figure 5
Effect of intraperitoneal administered simvastatin treatment on the survival of BALB/c mice infected with highly pathogenic avian influenza A/Vietnam/1203/2004 H5N1 virus. ***p < 0.001. beg.: Beginning; CMC: Carboxymethyl cellulose; q.d.: Once daily.
Figure 6
Figure 6
Effect of prolonged prophylaxis with simvastatin on survival of BALB/c mice infected with influenza A/Duck/MN/1525/81 H5N1 virus. ***p < 0.001. beg.: Beginning; b.i.d.: Two times a day; CMC: Carboxymethyl cellulose; q.d.: Once daily.
Figure 7
Figure 7
Effect of intraperitoneal administered rosuvastatin and atorvastatin on survival of BALB/c mice infected with influenza A/CA/04/09 H1N1pdm09 virus. ***p < 0.001 versus 0.4% CMC and PSS. b.i.d.: Two times a day; CMC: Carboxymethyl cellulose; PSS: Physiologically sterile saline; q.d.: Once daily.
Figure 8
Figure 8
Effect of orally administered statins on survival of BALB/c mice infected with influenza A/CA/04/09 H1N1pdm09 virus. ***p < 0.001 versus 0.4% CMC. beg.: Beginning; CMC: Carboxymethyl cellulose; q.d.: Once daily.
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