Abstract: Personal view
Antiviral effects of chloroquine
Effects of chloroquine on viral infections: an old
drug against today’s diseases?
Andrea Savarino, Johan R Boelaert, Antonio Cassone, Giancarlo Majori, and Roberto Cauda.
Chloroquine is a 9-aminoquinoline known since 1934. Apart
from its well-known antimalarial effects, the drug has
interesting biochemical properties that might be applied
against some viral infections. Chloroquine exerts direct
antiviral effects, inhibiting pH-dependent steps of the
replication of several viruses including members of the
flaviviruses, retroviruses, and coronaviruses. Its best-studied
effects are those against HIV replication, which are being
tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of
tumour necrosis factor and interleukin 6, which mediate the
inflammatory complications of several viral diseases. We
review the available information on the effects of chloroquine
on viral infections, raising the question of whether this old
drug may experience a revival in the clinical management of
viral diseases such as AIDS and severe acute respiratory
syndrome, which afflict mankind in the era of globalisation.
Endocytosis of viral particles
Transport of
endocytosed
virus
Virus
uncoating
Replication/
transcription
of viral
nucleic acids
Post-translational
processing
of envelope
glycoproteins
in the Golgi
Transport
of envelope
components
Assembly/
budding
Lancet Infect Dis 2003; 3: 722–27
Chloroquine is a 9-aminoquinoline that has been known
since 1934. Specifically synthesised to be used as an
antimalarial agent, chloroquine was subsequently shown to
have immunomodulatory properties that have encouraged
its application in the treatment of autoimmune diseases
such as rheumatoid arthritis. For this specific pathology,
chloroquine and its hydroxy-analogue hydroxychloroquine
have represented a valid contribution to the available
pharmacological tools, since they proved able to slow down
the progress of the disease while showing limited toxicity.1
Unfortunately, chloroquine is being gradually dismissed
from antimalarial therapy and prophylaxis, due to the
continuous emergence of chloroquine-resistant Plasmodium
falciparum strains. However, the tolerability, low cost, and
immunomodulatory properties of chloroquine/hydroxychloroquine are associated with biochemical effects that
suggest a potential use in viral infections, some of whose
symptoms may result from the inflammatory response.2,3 We
raise the question of whether this old drug whose parent
compound, quinine, was isolated in the late 19th century
from the bark of the tropical cinchona tree, may experience a
revival in the clinical management of viral diseases of the era
of globalisation.
General biochemical and cellular effects of
chloroquine
Both chloroquine and hydroxychloroquine are weak bases
that are known to affect acid vesicles leading to dysfunction
of several enzymes. Extracellularly, chloroquine/hydroxychloroquine is present mostly in a protonated form that, due
722
Transport of newly
formed viral particles
Assembly/budding
Exocytosis of viral particles
Figure 1. Steps of the replication of different viruses affected by
chloroquine (marked by red rectangles). Chloroquine inhibits the replication
of different viruses either at the early or late stages of viral replication.
to its positive charge, is incapable of crossing the plasma
membrane. However, the non-protonated..
{ 'indexed': {'date-parts': [[2024, 5, 14]], 'date-time': '2024-05-14T18:35:37Z', 'timestamp': 1715711737992},
'reference-count': 61,
'publisher': 'Elsevier BV',
'issue': '11',
'license': [ { 'start': { 'date-parts': [[2003, 11, 1]],
'date-time': '2003-11-01T00:00:00Z',
'timestamp': 1067644800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2003, 11]]},
'DOI': '10.1016/s1473-3099(03)00806-5',
'type': 'journal-article',
'created': { 'date-parts': [[2003, 10, 28]],
'date-time': '2003-10-28T04:21:37Z',
'timestamp': 1067314897000},
'page': '722-727',
'source': 'Crossref',
'is-referenced-by-count': 907,
'title': "Effects of chloroquine on viral infections: an old drug against today's diseases",
'prefix': '10.1016',
'volume': '3',
'author': [ {'given': 'Adrea', 'family': 'Savarino', 'sequence': 'first', 'affiliation': []},
{'given': 'John R', 'family': 'Boelaert', 'sequence': 'additional', 'affiliation': []},
{'given': 'Antonio', 'family': 'Cassone', 'sequence': 'additional', 'affiliation': []},
{'given': 'Giancario', 'family': 'Majori', 'sequence': 'additional', 'affiliation': []},
{'given': 'Roberto', 'family': 'Cauda', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'key': '10.1016/S1473-3099(03)00806-5_bib1',
'first-page': '2919',
'article-title': 'Canadian Consensus Conference on hydroxychloroquine',
'volume': '27',
'year': '2000',
'journal-title': 'J Rheumatol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib2',
'doi-asserted-by': 'crossref',
'first-page': '131',
'DOI': '10.1016/S1386-6532(00)00139-6',
'article-title': 'The anti-HIV-1 activity of chloroquine',
'volume': '20',
'author': 'Savarino',
'year': '2001',
'journal-title': 'J Clin Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib3',
'doi-asserted-by': 'crossref',
'first-page': '137',
'DOI': '10.1016/S1386-6532(00)00140-2',
'article-title': 'The potential place of chloroquine in the treatment of HIV-1–infected '
'patients',
'volume': '20',
'author': 'Boelaert',
'year': '2001',
'journal-title': 'J Clin Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib4',
'doi-asserted-by': 'crossref',
'first-page': '656',
'DOI': '10.1083/jcb.90.3.656',
'article-title': 'Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake '
'into lysosomes of weakly basic substances',
'volume': '90',
'author': 'Ohkuma',
'year': '1981',
'journal-title': 'J Cell Biol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib5',
'first-page': '212',
'article-title': 'Movements of vesicles in eukaryotic cells: role of intravesicle protons '
'as a fuel and modulation of their concentration by drugs or metabolic '
'changes',
'volume': '489',
'author': 'Pescarmona',
'year': '1998',
'journal-title': 'MRS Bull'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib6',
'doi-asserted-by': 'crossref',
'first-page': '1245',
'DOI': '10.1016/S0006-2952(00)00270-7',
'article-title': 'Reversal of MRP-mediated doxorubicin resistance with quinoline-based '
'drugs',
'volume': '59',
'author': 'Vezmar',
'year': '2000',
'journal-title': 'Biochem Pharmacol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib7',
'doi-asserted-by': 'crossref',
'first-page': '733',
'DOI': '10.1016/S0006-2952(98)00217-2',
'article-title': 'Direct binding of chloroquine to the multidrug resistance protein '
'(MRP): possible role for MRP in chloroquine drug transport and '
'resistance in tumor cells',
'volume': '56',
'author': 'Vezmar',
'year': '1998',
'journal-title': 'Biochem Pharmacol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib8',
'doi-asserted-by': 'crossref',
'first-page': '351',
'DOI': '10.1172/JCI115301',
'article-title': 'Chloroquine inhibits the intracellular multiplication of Legionella '
'pneumophila by limiting the availability of iron. A potential new '
'mechanism for the therapeutic effect of chloroquine against '
'intracellular pathogens',
'volume': '88',
'author': 'Byrd',
'year': '1991',
'journal-title': 'J Clin Invest'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib9',
'doi-asserted-by': 'crossref',
'first-page': '36',
'DOI': '10.1016/S0162-0134(02)00633-5',
'article-title': 'Changes in function of iron-loaded alveolar macrophages after in vivo '
'administration of desferrioxamine and/or chloroquine',
'volume': '94',
'author': 'Legssyer',
'year': '2003',
'journal-title': 'J Inorg Biochem'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib10',
'doi-asserted-by': 'crossref',
'first-page': '783',
'DOI': '10.1128/JVI.72.1.783-788.1998',
'article-title': 'Mechanism of Borna disease virus entry into cells',
'volume': '72',
'author': 'Gonzalez-Dunia',
'year': '1998',
'journal-title': 'J Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib11',
'doi-asserted-by': 'crossref',
'first-page': '12634',
'DOI': '10.1128/JVI.76.24.12634-12645.2002',
'article-title': 'Cytoplasmic trafficking of minute virus of mice: low-pH requirement, '
'routing to late endosomes, and proteasome interaction',
'volume': '76',
'author': 'Ros',
'year': '2002',
'journal-title': 'J Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib12',
'doi-asserted-by': 'crossref',
'first-page': '12866',
'DOI': '10.1128/JVI.76.24.12866-12876.2002',
'article-title': 'Endocytosis is a critical step in entry of subgroup B avian leukosis '
'viruses',
'volume': '76',
'author': 'Diaz-Griffero',
'year': '2000',
'journal-title': 'J Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib13',
'doi-asserted-by': 'crossref',
'first-page': '261',
'DOI': '10.1159/000024948',
'article-title': 'Examination of potential inhibitors of hepatitis A virus uncoating',
'volume': '41',
'author': 'Bishop',
'year': '1998',
'journal-title': 'Intervirology'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib14',
'doi-asserted-by': 'crossref',
'first-page': '313',
'DOI': '10.1099/0022-1317-49-4-313',
'article-title': 'Weak bases affect late stages of Mayaro virus replication cycle in '
'vertebrate cells',
'volume': '49',
'author': 'Ferreira',
'year': '2000',
'journal-title': 'J Med Microbiol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib15',
'doi-asserted-by': 'crossref',
'first-page': '1236',
'DOI': '10.1128/JVI.75.3.1236-1251.2001',
'article-title': 'Characterization of herpes simplex virus-containing organelles by '
'subcellular fractionation: role for organelle acidification in assembly '
'of infectious particles',
'volume': '75',
'author': 'Harley',
'year': '2001',
'journal-title': 'J Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib16',
'doi-asserted-by': 'crossref',
'first-page': '450',
'DOI': '10.1016/0042-6822(90)90099-D',
'article-title': 'Acidotropic amines inhibit proteolytic processing of flavivirus prM '
'protein',
'volume': '174',
'author': 'Randolph',
'year': '1990',
'journal-title': 'Virology'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib17',
'doi-asserted-by': 'crossref',
'first-page': '481',
'DOI': '10.1089/aid.1990.6.481',
'article-title': 'Inhibition of human immunodeficiency virus infectivity by chloroquine',
'volume': '6',
'author': 'Tsai',
'year': '1990',
'journal-title': 'AIDS Res Hum Retroviruses'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib18',
'doi-asserted-by': 'crossref',
'first-page': '1111',
'DOI': '10.1016/S0140-6736(03)12888-7',
'article-title': 'Sarcoidosis',
'volume': '361',
'author': 'Baughman',
'year': '2003',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib19',
'doi-asserted-by': 'crossref',
'first-page': '4901',
'DOI': '10.4049/jimmunol.158.10.4901',
'article-title': 'Chloroquine inhibits processing of tumor necrosis factor in '
'lipopolysaccharidestimulated RAW 264·7 macrophages',
'volume': '158',
'author': 'Jeong',
'year': '1997',
'journal-title': 'J Immunol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib20',
'doi-asserted-by': 'crossref',
'first-page': '357',
'DOI': '10.1016/S0306-3623(97)00269-3',
'article-title': 'Antimalarial drugs inhibit phospholipase A2 activation and induction of '
'interleukinβ and tumor necrosis factor α in macrophages',
'volume': '30',
'author': 'Bondeson',
'year': '1998',
'journal-title': 'General Pharmacol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib21',
'first-page': '55',
'article-title': 'Chloroquine and hydroxychloroquine equally affect tumor necrosis '
'factor-α, interleukin 6 and interferon-γ production by peripheral blood '
'mononuclear cells',
'volume': '24',
'author': 'Van den Borne',
'year': '1997',
'journal-title': 'J Rheumatol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib22',
'first-page': 'R1058',
'article-title': 'Chloroquine inhibits proinflammatory cytokine release into human whole '
'blood',
'volume': '274',
'author': 'Karres',
'year': '1998',
'journal-title': 'Am J Physiol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib23',
'first-page': '127',
'article-title': 'Chloroquine-induced inhibition of the production of TNF, but not of '
'IL-6, is affected by disruption of iron metabolism',
'volume': '80',
'author': 'Picot',
'year': '1993',
'journal-title': 'Immunology'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib24',
'doi-asserted-by': 'crossref',
'first-page': '1534',
'DOI': '10.4049/jimmunol.165.3.1534',
'article-title': 'Chloroquine interferes with lipopolysaccharide-induced TNF-α gene '
'expression by a nonlysosomotropic mechanism',
'volume': '165',
'author': 'Weber',
'year': '2000',
'journal-title': 'J Immunol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib25',
'doi-asserted-by': 'crossref',
'first-page': '83',
'DOI': '10.1046/j.0019-2805.2001.01339.x',
'article-title': 'Chloroquine decreases cell-surface expression of tumour necrosis factor '
'receptors in human histiocytic U-937 cells',
'volume': '105',
'author': 'Jeong',
'year': '2002',
'journal-title': 'Immunol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib26',
'doi-asserted-by': 'crossref',
'first-page': '235',
'DOI': '10.1080/09629350020025755',
'article-title': 'Permeability characteristics of human endothelial monolayers seeded on '
'different extracellular matrix proteins',
'volume': '9',
'author': 'Nooteboom',
'year': '2000',
'journal-title': 'Mediators Inflamm'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib27',
'first-page': '292',
'article-title': 'Ocular safety of hydroxychloroquine',
'volume': '23',
'author': 'Bernstein',
'year': '1991',
'journal-title': 'Ann Ophthalmol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib28',
'doi-asserted-by': 'crossref',
'first-page': '25',
'DOI': '10.1016/0002-9343(83)91267-6',
'article-title': 'Ophthalmologic considerations and testing in patients receiving '
'long-term antimalarial therapy',
'volume': '75',
'author': 'Bernstein',
'year': '1983',
'journal-title': 'Am J Med'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib29',
'first-page': '21',
'article-title': '(Hydroxy)-chloroquine retinal toxicity: two case reports and safety '
'guidelines',
'volume': '284',
'author': 'Herman',
'year': '2002',
'journal-title': 'Bull Soc Belge Ophtalmol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib30',
'doi-asserted-by': 'crossref',
'first-page': '813',
'DOI': '10.1016/S0140-6736(01)06004-4',
'article-title': 'Ocular toxicity and antenatal exposure to chloroquine or '
'hydroxychloroquine for rheumatic diseases',
'volume': '358',
'author': 'Klinger',
'year': '2001',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib31',
'doi-asserted-by': 'crossref',
'first-page': '91',
'DOI': '10.1089/aid.1993.9.91',
'article-title': 'Inhibition of human immunodeficiency virus type 1 replication by '
'hydroxychloroquine in T cells and monocytes',
'volume': '9',
'author': 'Sperber',
'year': '1993',
'journal-title': 'AIDS Res Hum Retroviruses'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib32',
'doi-asserted-by': 'crossref',
'first-page': '45',
'DOI': '10.1016/S0165-2478(98)00096-0',
'article-title': 'Chloroquine inhibits HIV-1 replication in human peripheral blood '
'lymphocytes',
'volume': '64',
'author': 'Pardridge',
'year': '1998',
'journal-title': 'Immunol Lett'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib33',
'doi-asserted-by': 'crossref',
'first-page': '2221',
'DOI': '10.1097/00002030-200111230-00002',
'article-title': 'Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum '
'of activity',
'volume': '15',
'author': 'Savarino',
'year': '2001',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib34',
'doi-asserted-by': 'crossref',
'first-page': '622',
'DOI': '10.1016/0149-2918(95)80039-5',
'article-title': 'Hydroxychloroquine treatment of patients with human immunodeficiency '
'virus type 1',
'volume': '17',
'author': 'Sperber',
'year': '1995',
'journal-title': 'Clin Ther'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib35',
'doi-asserted-by': 'crossref',
'first-page': '913',
'DOI': '10.1016/S0149-2918(97)80045-8',
'article-title': 'Comparison of hydroxychloroquine with zidovudine in asymptomatic '
'patients infected with HIV-1',
'volume': '19',
'author': 'Sperber',
'year': '1997',
'journal-title': 'Clin Ther'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib36',
'unstructured': 'Debiaggi M, Bruno R, Sacchi P, Filice G. Antiviral activity of '
'chloroquine against HIV-1 strains resistant to antiretroviral drugs. '
'Antiviral Res (in press)'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib37',
'doi-asserted-by': 'crossref',
'first-page': '1080',
'DOI': '10.1016/S0149-2918(96)80063-4',
'article-title': 'Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of '
'action and comparison with zidovudine',
'volume': '18',
'author': 'Chiang',
'year': '1996',
'journal-title': 'Clin Ther'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib38',
'doi-asserted-by': 'crossref',
'first-page': '1224',
'DOI': '10.1016/S0140-6736(05)60566-1',
'article-title': 'Antiretroviral therapy',
'volume': '352',
'author': 'Boelaert JR and Sperber',
'year': '1998',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib39',
'doi-asserted-by': 'crossref',
'first-page': '1531',
'DOI': '10.1016/S0006-2952(01)00576-7',
'article-title': 'Chloroquine exerts an additive in vitro anti-HIV-1 effect, when '
'combined to zidovudine and hydroxyurea',
'volume': '61',
'author': 'Boelaert',
'year': '2001',
'journal-title': 'Biochem Pharmacol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib40',
'doi-asserted-by': 'crossref',
'first-page': '1667',
'DOI': '10.1016/S0140-6736(02)08557-4',
'article-title': 'Hydroxychloroquine, hydroxycarbamide, and didanosine as economic '
'treatment for HIV-1',
'volume': '359',
'author': 'Paton',
'year': '2002',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib41',
'doi-asserted-by': 'crossref',
'first-page': '2221',
'DOI': '10.1097/00002030-200211080-00016',
'article-title': 'The boosting of didanosine by allopurinol permits a halving of the '
'didanosine dosage',
'volume': '16',
'author': 'Boelaert',
'year': '2002',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib42',
'doi-asserted-by': 'crossref',
'first-page': '2237',
'DOI': '10.1016/S0140-6736(00)02415-6',
'article-title': 'Advances and research directions in the prevention of mother-to-child '
'HIV-1 transmission',
'volume': '355',
'author': 'Mofenson',
'year': '2000',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib43',
'doi-asserted-by': 'crossref',
'first-page': '2205',
'DOI': '10.1097/00002030-200111090-00024',
'article-title': 'Chloroquine accumulates in breast milk cells. Potential impact as '
'adjuvant to antiretroviral prophylaxis for postnatal mother-to-child '
'transmission of HIV-1',
'volume': '15',
'author': 'Boelaert',
'year': '2001',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib44',
'doi-asserted-by': 'crossref',
'first-page': '1175',
'DOI': '10.1001/jama.283.9.1175',
'article-title': 'Prevention of mother-to-child transmission of HIV-1 in resource-poor '
'countries: translating research into policy and practice',
'volume': '283',
'author': 'DeCock',
'year': '2000',
'journal-title': 'JAMA'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib45',
'doi-asserted-by': 'crossref',
'first-page': '2177',
'DOI': '10.1016/S0140-6736(02)09095-5',
'article-title': 'HIV-1/AIDS and the control of other infectious diseases in Africa',
'volume': '359',
'author': 'Corbett',
'year': '2002',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib46',
'doi-asserted-by': 'crossref',
'first-page': '2083',
'DOI': '10.1097/00002030-200009290-00003',
'article-title': 'Immune activation in Africa is environmentally driven and is associated '
'with upregulation of CCR5',
'volume': '14',
'author': 'Clerici',
'year': '2000',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib47',
'doi-asserted-by': 'crossref',
'first-page': '2071',
'DOI': '10.1097/00002030-200009290-00002',
'article-title': 'Concurrent infections and HIV pathogenesis',
'volume': '14',
'author': 'Bentwich',
'year': '2000',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib48',
'doi-asserted-by': 'crossref',
'first-page': '76',
'DOI': '10.1086/315185',
'article-title': 'Elevated tumor necrosis factor-α activation of human immunodeficiency '
'virus subtype 1 in southern Africa is associated with an NF-kB enhancer '
'gain-of-function',
'volume': '181',
'author': 'Montano',
'year': '2000',
'journal-title': 'J Infect Dis'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib49',
'doi-asserted-by': 'crossref',
'first-page': '1995',
'DOI': '10.1056/NEJMoa030634',
'article-title': 'Identification of severe acute respiratory syndrome in Canada',
'volume': '348',
'author': 'Poutanen',
'year': '2003',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib50',
'doi-asserted-by': 'crossref',
'first-page': '1615',
'DOI': '10.1016/S0140-6736(03)13265-5',
'article-title': 'Development of a standard treatment protocol for severe acute '
'respiratory syndrome',
'volume': '361',
'author': 'So',
'year': '2003',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib51',
'doi-asserted-by': 'crossref',
'first-page': '1319',
'DOI': '10.1016/S0140-6736(03)13077-2',
'article-title': 'Coronavirus as a possible cause of severe acute respiratory syndrome',
'volume': '361',
'author': 'Peiris',
'year': '2003',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib52',
'doi-asserted-by': 'crossref',
'first-page': '1967',
'DOI': '10.1056/NEJMoa030747',
'article-title': 'Identification of a novel coronavirus in patients with severe acute '
'respiratory syndrome',
'volume': '348',
'author': 'Drosten',
'year': '2003',
'journal-title': 'N Engl J Med'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib53',
'series-title': 'The Nidoviruses, Coronaviruses and Arteriviruses',
'first-page': '193',
'article-title': 'Human Coronavirus HCoV-229E enters susceptible cells via the endocytic '
'pathway',
'author': 'Blau',
'year': '2001'},
{ 'issue': 'Pt 2',
'key': '10.1016/S1473-3099(03)00806-5_bib54',
'doi-asserted-by': 'crossref',
'first-page': '297',
'DOI': '10.1099/0022-1317-80-2-297',
'article-title': 'Entry of porcine reproductive and respiratory syndrome virus into '
'porcine alveolar macrophages via receptor-mediated endocytosis',
'volume': '80',
'author': 'Nauwynck',
'year': '1999',
'journal-title': 'J Gen Virol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib55',
'doi-asserted-by': 'crossref',
'first-page': '1767',
'DOI': '10.1016/S0140-6736(03)13412-5',
'article-title': 'Clinical progression and viral load in a community outbreak of '
'coronavirus-associated SARS pneumonia: a prospective study',
'volume': '361',
'author': 'Peiris',
'year': '2003',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib56',
'doi-asserted-by': 'crossref',
'first-page': '40',
'DOI': '10.1016/1357-4310(95)80019-0',
'article-title': 'The role of cytokines and adhesion molecules in the development of '
'inflammatory injury',
'volume': '1',
'author': 'Shanley',
'year': '1995',
'journal-title': 'Mol Med Today'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib57',
'doi-asserted-by': 'crossref',
'first-page': '1773',
'DOI': '10.1016/S0140-6736(03)13413-7',
'article-title': 'Lung pathology of fatal severe acute respiratory syndrome',
'volume': '361',
'author': 'Nicholls',
'year': '2003',
'journal-title': 'Lancet'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib58',
'doi-asserted-by': 'crossref',
'first-page': '161',
'DOI': '10.1016/S0165-2427(02)00047-8',
'article-title': 'In vivo studies on cytokine involvement during acute viral respiratory '
'disease of swine: troublesome but rewarding',
'volume': '87',
'author': 'Van Reeth',
'year': '2002',
'journal-title': 'Vet Immunol Immunopathol'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib59',
'doi-asserted-by': 'crossref',
'first-page': '312',
'DOI': '10.1086/321889',
'article-title': 'Risks factors and prevention of Q fever endocarditis',
'volume': '33',
'author': 'Fenollar',
'year': '2001',
'journal-title': 'Clin Infect Dis'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib60',
'doi-asserted-by': 'crossref',
'first-page': '275',
'DOI': '10.1097/00002030-200301240-00025',
'article-title': 'Malaria, HIV and pregnancy',
'volume': '17',
'author': 'Ladner',
'year': '2003',
'journal-title': 'AIDS'},
{ 'key': '10.1016/S1473-3099(03)00806-5_bib61',
'doi-asserted-by': 'crossref',
'first-page': '1079',
'DOI': '10.1097/00002030-200006160-00004',
'article-title': 'Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation '
'or an active player in virus/host interactions?',
'volume': '14',
'author': 'Savarino',
'year': '2000',
'journal-title': 'AIDS'}],
'container-title': 'The Lancet Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S1473309903008065?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S1473309903008065?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2023, 4, 27]],
'date-time': '2023-04-27T08:30:22Z',
'timestamp': 1682584222000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S1473309903008065'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2003, 11]]},
'references-count': 61,
'journal-issue': {'issue': '11', 'published-print': {'date-parts': [[2003, 11]]}},
'alternative-id': ['S1473309903008065'],
'URL': 'http://dx.doi.org/10.1016/S1473-3099(03)00806-5',
'relation': {},
'ISSN': ['1473-3099'],
'subject': [],
'container-title-short': 'The Lancet Infectious Diseases',
'published': {'date-parts': [[2003, 11]]}}
