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
www.nature.com/cr
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 (http://www.who.int/influenza/preparedness/pandemic/h5n1phase/en/index.html). 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..
{ 'indexed': {'date-parts': [[2024, 5, 14]], 'date-time': '2024-05-14T21:57:00Z', 'timestamp': 1715723820072},
'reference-count': 13,
'publisher': 'Springer Science and Business Media LLC',
'issue': '2',
'license': [ { 'start': { 'date-parts': [[2012, 12, 4]],
'date-time': '2012-12-04T00:00:00Z',
'timestamp': 1354579200000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'http://www.springer.com/tdm'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2013, 2]]},
'DOI': '10.1038/cr.2012.165',
'type': 'journal-article',
'created': {'date-parts': [[2012, 12, 4]], 'date-time': '2012-12-04T11:42:13Z', 'timestamp': 1354621333000},
'page': '300-302',
'source': 'Crossref',
'is-referenced-by-count': 238,
'title': 'Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus '
'infection in an animal model',
'prefix': '10.1038',
'volume': '23',
'author': [ {'given': 'Yiwu', 'family': 'Yan', 'sequence': 'first', 'affiliation': []},
{'given': 'Zhen', 'family': 'Zou', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yang', 'family': 'Sun', 'sequence': 'additional', 'affiliation': []},
{'given': 'Xiao', 'family': 'Li', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kai-Feng', 'family': 'Xu', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yuquan', 'family': 'Wei', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ningyi', 'family': 'Jin', 'sequence': 'additional', 'affiliation': []},
{'given': 'Chengyu', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2012, 12, 4]]},
'reference': [ { 'key': 'BFcr2012165_CR1',
'doi-asserted-by': 'crossref',
'unstructured': 'Herfst S, Schrauwen EJ, Linster M, et al. Science 2012; 336:1534–1541.',
'DOI': '10.1126/science.1213362'},
{ 'key': 'BFcr2012165_CR2',
'doi-asserted-by': 'crossref',
'unstructured': 'Imai M, Watanabe T, Hatta M, et al. Nature 2012; 486:420–428.',
'DOI': '10.1038/nature10831'},
{ 'key': 'BFcr2012165_CR3',
'doi-asserted-by': 'crossref',
'unstructured': 'Enserink M . Science 2011; 334:1192–1193.',
'DOI': '10.1126/science.334.6060.1192'},
{ 'key': 'BFcr2012165_CR4',
'doi-asserted-by': 'crossref',
'unstructured': 'Bauer TT, Ewig S, Rodloff AC, et al. Clin Infect Dis 2006; 43:748–756.',
'DOI': '10.1086/506430'},
{ 'key': 'BFcr2012165_CR5',
'doi-asserted-by': 'crossref',
'unstructured': 'Wang H, Jiang C . Sci China C Life Sci 2009; 52:459–463.',
'DOI': '10.1007/s11427-009-0059-7'},
{ 'key': 'BFcr2012165_CR6',
'doi-asserted-by': 'crossref',
'unstructured': 'Sun Y, Li C, Shu Y, et al. Sci Signal 2012; 5:ra16.',
'DOI': '10.1126/scisignal.2001931'},
{ 'key': 'BFcr2012165_CR7',
'doi-asserted-by': 'crossref',
'unstructured': 'Carew JS, Espitia CM, Esquivel JA 2nd, et al. J Biol Chem 2011; '
'286:6602–6613.',
'DOI': '10.1074/jbc.M110.151324'},
{ 'key': 'BFcr2012165_CR8',
'doi-asserted-by': 'crossref',
'unstructured': 'Solomon VR, Lee H . Eur J Pharmacol 2009; 625:220–233.',
'DOI': '10.1016/j.ejphar.2009.06.063'},
{ 'key': 'BFcr2012165_CR9',
'doi-asserted-by': 'crossref',
'unstructured': 'Kim J, Yip ML, Shen X, et al. PLoS One 2012; 7:e 31004.',
'DOI': '10.1371/journal.pone.0031004'},
{ 'key': 'BFcr2012165_CR10',
'doi-asserted-by': 'crossref',
'unstructured': 'Savarino A . Lancet Infect Dis 2011; 11:653–654.',
'DOI': '10.1016/S1473-3099(11)70092-5'},
{ 'key': 'BFcr2012165_CR11',
'doi-asserted-by': 'crossref',
'unstructured': 'Wang H, Jiang C . Sci China C Life Sci 2009; 52:464–469.',
'DOI': '10.1007/s11427-009-0061-0'},
{ 'key': 'BFcr2012165_CR12',
'doi-asserted-by': 'crossref',
'unstructured': 'Paton NI, Lee L, Xu Y, et al. Lancet Infect Dis 2011; 11:677–683.',
'DOI': '10.1016/S1473-3099(11)70065-2'},
{ 'key': 'BFcr2012165_CR13',
'doi-asserted-by': 'crossref',
'unstructured': 'Lund J, Sato A, Akira S, et al. J Exp Med 2003; 198:513–520.',
'DOI': '10.1084/jem.20030162'}],
'container-title': 'Cell Research',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'http://www.nature.com/articles/cr2012165.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'http://www.nature.com/articles/cr2012165',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'http://www.nature.com/articles/cr2012165.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 5, 18]],
'date-time': '2023-05-18T13:31:16Z',
'timestamp': 1684416676000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.nature.com/articles/cr2012165'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2012, 12, 4]]},
'references-count': 13,
'journal-issue': {'issue': '2', 'published-print': {'date-parts': [[2013, 2]]}},
'alternative-id': ['BFcr2012165'],
'URL': 'http://dx.doi.org/10.1038/cr.2012.165',
'relation': {},
'ISSN': ['1001-0602', '1748-7838'],
'subject': [],
'container-title-short': 'Cell Res',
'published': {'date-parts': [[2012, 12, 4]]}}
