Protective effect of fluvastatin on influenza virus infection

Peng,Jing; Zhang,Dingmei; Ma,Yu; Wang,Guoling; Guo,Zhongmin; Lu,Jiahai

doi:10.3892/mmr.2014.2076

Protective effect of fluvastatin on influenza virus infection

Authors:
- Jing Peng
- Dingmei Zhang
- Yu Ma
- Guoling Wang
- Zhongmin Guo
- Jiahai Lu
View Affiliations

Affiliations: School of Public Health, State Ministry of Education, Key Laboratory of Tropical Diseases Control Research, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Haizhu Center for Disease Control and Prevention, Guangzhou, Guangdong 510288, P.R. China, Experimental Animal Center, Sun Yat‑sen University, Guangzhou, Guangdong 510080, PR China
Published online on: March 27, 2014 https://doi.org/10.3892/mmr.2014.2076
Pages: 2221-2226

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Statins are 3‑hydroxy‑3‑methylglutaryl coenzyme A reductase inhibitors and have pleiotropic effects. It has been suggested that statins may be a potential treatment during the next influenza pandemic. In a previous study we found that a statin/caffeine combination protects BALB/c mice against Influenza A, subtypes haemagglutinin type 5 and neuraminidase type 1 (H5N1), H3N2 and H1N1 infection. The effect of statins alone on influenza virus infection, however, is not known. In this study, it was investigated whether fluvastatin is capable of inhibiting influenza A virus replication in vitro. The results demonstrated that the synthesis of viral RNA and protein was affected by fluvastatin treatment. Virus production was markedly reduced when fluvastatin was administered simultaneously with the virus; however, a greater inhibition was observed when fluvastatin was added following viral adsorption. The selectivity index [SI; 50% cytotoxic concentration (CC50)/50% inhibition concentration (IC50)], however, was only 21. It was further demonstrated that fluvastatin protects host cells against influenza‑induced inflammation by reducing the production of tumour necrosis factor‑α, interleukin 8 and interferon γ. In conclusion, the results demonstrated that fluvastatin exerted a minor inhibitory effect on influenza virus infection, which involved anti‑inflammatory activities.

View Figures

View References

1	Kok J and Dwyer DE: How common was 2009 pandemic influenza A H1N1? Lancet Infect Dis. 11:423–424. 2011. View Article : Google Scholar : PubMed/NCBI
2	World Health Organization. Pandemic (H1N1) - update 112. http://www.who.int/csr/don/2010_08_06/en/indexhtml. Accessed November 10, 2011
3	Memoli MJ, Morens DM and Taubenberger JK: Pandemic and seasonal influenza: therapeutic challenges. Drug Discov Today. 13:590–595. 2008. View Article : Google Scholar : PubMed/NCBI
4	Cox MM: Pandemic influenza: overview of vaccines and antiviral drugs. Yale J Biol Med. 78:321–328. 2005.PubMed/NCBI
5	Podolec P and Kopeć G: Influenza vaccines for prevention of cardiovascular diseases. Kardiol Pol. 65:612–615. 2007.(In Polish).
6	Lambert LC and Fauci AS: Influenza vaccines for the future. N Engl J Med. 363:2036–2044. 2010. View Article : Google Scholar : PubMed/NCBI
7	Sugrue RJ, Tan BH, Yeo DS and Sutejo R: Antiviral drugs for the control of pandemic influenza virus. Ann Acad Med Singapore. 37:518–524. 2008.PubMed/NCBI
8	Moss RB, Davey RT, Steigbigel RT and Fang F: Targeting pandemic influenza: a primer on influenza antivirals and drug resistance. J Antimicrob Chemother. 65:1086–1093. 2010. View Article : Google Scholar : PubMed/NCBI
9	Fedson DS: Confronting an influenza pandemic with inexpensive generic agents: can it be done? Lancet Infect Dis. 8:571–576. 2008. View Article : Google Scholar : PubMed/NCBI
10	Tleyjeh IM, Kashour T, Hakim FA, et al: Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med. 169:1658–1667. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zhou Q and Liao JK: Pleiotropic effects of statins: basic research and clinical perspectives. Circ J. 74:818–826. 2010. View Article : Google Scholar : PubMed/NCBI
12	Corsini A, Ferri N and Cortellaro M: Are pleiotropic effects of statins real? Vasc Health Risk Manag. 3:611–613. 2007.PubMed/NCBI
13	Terblanche M, Smith TS and Adhikari NK: Statins, bugs and prophylaxis: intriguing possibilities. Crit Care. 10:1682006. View Article : Google Scholar : PubMed/NCBI
14	Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR and Katze MG: Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 76:16–32. 2012. View Article : Google Scholar : PubMed/NCBI
15	Montoya CJ, Jaimes F, Higuita EA, et al: Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial. Trials. 10:412009. View Article : Google Scholar
16	Gower TL and Graham BS: Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro. Antimicrob Agents Chemother. 45:1231–1237. 2001. View Article : Google Scholar : PubMed/NCBI
17	Frost FJ, Petersen H, Tollestrup K and Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest. 131:1006–1012. 2007. View Article : Google Scholar : PubMed/NCBI
18	Kwong JC, Li P and Redelmeier DA: Influenza morbidity and mortality in elderly patients receiving statins: a cohort study. PLoS One. 4:e80872009. View Article : Google Scholar : PubMed/NCBI
19	Hayden F: Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis. 48(Suppl 1): S3–S13. 2009. View Article : Google Scholar : PubMed/NCBI
20	Nair P and Roguin A: Statins and the acute coronary syndrome: ‘the early bird catches the worm’. Int J Clin Pract. 60:716–727. 2006.
21	Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL and Gale M Jr: Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Nat Acad Sci USA. 100:15865–15870. 2003. View Article : Google Scholar : PubMed/NCBI
22	del Real G, Jiménez-Baranda S, Mira E, et al: Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 200:541–547. 2004.PubMed/NCBI
23	Moncunill G, Negredo E, Bosch L, et al: Evaluation of the anti-HIV activity of statins. AIDS. 19:1697–1700. 2005. View Article : Google Scholar : PubMed/NCBI
24	Janssen NE, van Lelyveld SF, Hoepelman AI, Gras L, Groenwold RH and Oosterheert JJ: The effect of statin therapy on pneumonia in an HIV-infected population in the Netherlands. J Infect. 67:238–241. 2013. View Article : Google Scholar : PubMed/NCBI
25	Grau AC and George SM: Improved outcomes in community-acquired pneumonia with prior statin use. Am J Med. 122:e15author reply e17. 2009. View Article : Google Scholar : PubMed/NCBI
26	Chalmers JD, Singanayagam A, Murray MP and Hill AT: Prior statin use is associated with improved outcomes in community-acquired pneumonia. Am J Med. 121:1002–1007. 2008. View Article : Google Scholar : PubMed/NCBI
27	Guo YF and Hu DY: Statin use and reduced prevalence of sepsis. Zhonghua Nei Ke Za Zhi. 46:798–800. 2007.(In Chinese).
28	Almog Y, Shefer A, Novack V, et al: Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 110:880–885. 2004. View Article : Google Scholar : PubMed/NCBI
29	Liu Z, Guo Z, Wang G, et al: Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice. Eur J Pharm Sci. 38:215–223. 2009. View Article : Google Scholar : PubMed/NCBI
30	Jin Y, Zhang G, Hu Y, et al: Inhibition of highly pathogenic avian H5N1 influenza virus propagation by RNA oligonucleotides targeting the PB2 gene in combination with celecoxib. J Gene Med. 13:243–249. 2011. View Article : Google Scholar : PubMed/NCBI
31	Hui DS, Lee N and Chan PK: Adjunctive therapies and immunomodulatory agents in the management of severe influenza. Antiviral Res. 98:410–416. 2013. View Article : Google Scholar : PubMed/NCBI
32	Node K, Fujita M, Kitakaze M, Hori M and Liao JK: Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 108:839–843. 2003. View Article : Google Scholar : PubMed/NCBI
33	Radigan KA, Urich D, Misharin AV, et al: The effect of rosuvastatin in a murine model of influenza A infection. PLoS One. 7:e357882012. View Article : Google Scholar : PubMed/NCBI
34	Belser JA, Szretter KJ, Katz JM and Tumpey TM: Simvastatin and oseltamivir combination therapy does not improve the effectiveness of oseltamivir alone following highly pathogenic avian H5N1 influenza virus infection in mice. Virology. 439:42–46. 2013. View Article : Google Scholar : PubMed/NCBI
35	Zarogiannis SG, Noah JW, Jurkuvenaite A, Steele C, Matalon S and Noah DL: Comparison of ribavirin and oseltamivir in reducing mortality and lung injury in mice infected with mouse adapted A/California/04/2009 (H1N1). Life Sci. 90:440–445. 2012. View Article : Google Scholar : PubMed/NCBI