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Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model

Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165
Dec 2012  
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CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
Yan et al., 4 Dec 2012, peer-reviewed, 8 authors.
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Abstract: npg CQ ameliorates acute lung injury induced by H5N1 virus 300 LETTER TO THE EDITOR Cell Research (2013) 23:300-302. © 2013 IBCB, SIBS, CAS All rights reserved 1001-0602/13 $ 32.00 Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model Cell Research (2013) 23:300-302. doi:10.1038/cr.2012.165; published online 4 December 2012 Dear Editor, The recent controversial studies of man-made avian flu viruses caused a media storm, and brought new concerns to the potential of an avian influenza H5N1 virus pandemic, which has been pending since 1997 [1, 2]. Although the estimated mortality rate of avian influenza A H5N1 virus infection in humans could be as high as 60%, the World Health Organization (WHO) phase of pandemic alert is currently set at 3, due to that there has not been human-to-human or community-level transmission ( However, the newly created H5N1 virus strains, which are genetically altered, are transmissible among ferrets, and thus may trigger a real pandemic that could potentially result in millions of deaths according to Science Insider [3]. While it is arguably a bit too late to debate whether regulations or mandatory reviews should be applied to these dualuse studies, in the matter of fact, these viruses that are probably among the most dangerous infectious agents known already exist. Therefore, a top priority at present is to find effective prophylactic or therapeutic agents that would help to control a pandemic of avian influenza A H5N1 viruses. Previous reports have demonstrated that the high mortality in humans infected with avian influenza A H5N1 is partly due to acute lung injury or the resulting severe condition, acute respiratory distress syndrome (ARDS) [4, 5]. There are few treatment choices for ARDS, aside from mechanical supporting equipment and empirical treatments. The use of cortisones is controversial. We have recently discovered that avian influenza A H5N1 virus infection causes acute lung injury by inducing autophagic alveolar epithelial cell death [6]. Importantly, we found that autophagy inhibitors are effective in ameliorating murine acute lung injury induced by live avian influenza A H5N1 virus infections [6]. We thus hypothesize that if a drug that is currently in clinical use can act to inhibit autophagy, then such a drug might be a good candidate for treating H5N1 infections. To test this, we have focused our efforts on chloroquine (CQ), as CQ is the only oral clinical drug that is known to be an autophagy inhibitor [7]. CQ, or N′-(7chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and his coworkers at Bayer Laboratories and was introduced into clinical practice in 1947 as a prophylactic treatment for malaria [8]. Currently, CQ and its hydroxyl form, HCQ, are used as anti-inflammatory agents for the treatment of rheumatoid arthritis, lupus erythematosus and amoebic hepatitis. More recently, CQ has been studied for its potential use as an enhancing agent in cancer therapies as well as novel antagonists to chemokine receptor CXCR4 in pancreatic cancer [8, 9]. We first tested whether CQ could inhibit cell death in the human lung carcinoma A549 cells infected with live avian influenza A H5N1 virus. The cell viability was improved both prophylactically and therapeutically in a dose-dependent manner with..
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