In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect
Julien Andreani, Marion Le Bideau, Isabelle Duflot, Priscilla Jardot, Clara Rolland, Manon Boxberger, Nathalie Wurtz, Jean-Marc Rolain, Philippe Colson, Bernard La Scola, Didier Raoult
Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
Author statement Virus culture and drug testing: JA, ML, ID, NW; Molecular biology testing: PJ, CR, MB; Analyzed the results: JA, JMR, PC, BL, DR; Wrote the manuscript: JA, BL; Conceived the study: BL, DR. Pictures were captured on ZEISS AxioCam ERC 5s, 58 h post infection. Magnitude X200.3A-B-C. overview of the monolayer in each well for the condition of azithromycin 5 μM associated with hydroxychloroquine at 5 μM, 3D. Negative control well and 3E. Positive control well. 1F. Observation was done 48 h post infection by the SARS-CoV 2 strain IHUMI-3 for the viral stock production. Magnitude X400.
Declaration of competing interest Authors would like to declare that Didier Raoult is a consultant in microbiology for Hitachi High-Tech Corporation. Funding sources had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The others authors declare no conflict of interest.
References
Amrane, Tissot-Dupont, Doudier, Eldin, Hocquart et al., Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infections diseases referral hospital in Marseille, France, -January 31st to March 1st, 2020: a respiratory virus snapshot, Trav. Med. Infect. Dis,
doi:10.1016/j.tmaid.2020.101663Armstrong, Richez, Raoult, Chabriere, Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease, J. Chromatogr. B Analyt Technol. Biomed. Life Sci
Bosseboeuf, Aubry, Nhan, De Pina, Rolain et al., Azithromycin inhibits the replication of Zika virus, J. Antivir. Antiretrovir
Boulos, Rolain, Raoult, Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells, Antimicrob. Agents Chemother
Chen, Lau, Lamirande, Paddock, Bartlett et al., Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection, J Virol
Colson, Rolain, Lagier, Brouqui, Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, Int. J. Antimicrob. Agents
De Wilde, Jochmans, Posthuma, Zevenhoven-Dobbe, Van et al., Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture, Antimicrob. Agents Chemother
Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int. J. Antimicrob. Agents
Fenollar, Puechal, Raoult, Whipple's disease, N. Engl. J. Med
Fleming-Dutra, Demirjian, Bartoces, Roberts, Taylor et al., Variations in antibiotic and azithromycin prescribing for children by geography and specialty-United States, 2013, Pediatr. Infect. Dis. J
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci. Trends
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int. J. Antimicrob. Agents
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2002032Keyaerts, Li, Vijgen, Rysman, Verbeeck et al., Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice, Antimicrob. Agents Chemother
Keyaerts, Vijgen, Maes, Neyts, Van, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem. Biophys. Res. Commun
Kn Lusamba, Nomura, Kawase, Ota, Kubo et al., The non-antibiotic macrolide EM900 inhibits rhinovirus infection and cytokine production in human airway epithelial cells, Physiol Rep
Kn Lusamba, Nomura, Kawase, Ota, Kubo et al., The non-antibiotic macrolide EM900 inhibits rhinovirus infection and cytokine production in human airway epithelial cells, Physiol Rep
Kono, Tatsumi, Imai, Saito, Kuriyama et al., Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK, Antivir. Res
Kruse, Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan
Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges, Int. J. Antimicrob. Agents
Li, Zu, Deng, Li, Parvatiyar et al., Azithromycin protects against Zika virus infection by upregulating virus-induced type I and III interferon responses, Antimicrob. Agents Chemother,
doi:10.1128/AAC.00394-19Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Livak, Schmittgen, Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods
Mf Morgene, Maurin, Pillet, Berthelot, Morfin et al., HaCaT epithelial cells as an innovative novel model of rhinovirus infection and impact of clarithromycin treatment on infection kinetics, Virology
Morens, Folkers, Fauci, What is a pandemic?, J. Infect. Dis
Nabirothckin, Peluffo, Bouaziz, Cohen, Focusing on the unfolded protein response and autophagy related pathways to reposition common approved drugs against COVID-19,
doi:10.20944/preprints202003.0302.v1Ohkuma, Poole, Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH various agents, Proc. Natl. Acad. Sci. U.S.A
Raoult, Drancourt, Vestris, Bactericidal effect of Doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells, Antimicrob. Agents Chemother
Raoult, Houpikian, Tissot-Dupont, Riss, Arditi-Djiane et al., Treatment of Q fever endocarditis : comparison of two regimens containing doxycycline and ofloxacin or hydroxychloroquine, Arch. Intern. Med
Retallack, Di, Arias, Knopp, Laurie et al., Zika virus cell tropism in the developing human brain and inhibition by azithromycin, Proc. Natl. Acad. Sci. U. S. A
Rothe, Schunk, Sothmann, Bretzel, Froeschl et al., Transmission of 2019-nCoV infection from an asymptomatic contact in Germany, N. Engl. J. Med
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect. Dis
Vabret, Dina, Gouarin, Petitjean, Tripey et al., Human (non-severe acute respiratory syndrome) coronavirus infections in hospitalised children in France, J. Paediatr. Child Health
Vincent, Bergeron, Benjannet, Erickson, Rollin et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol. J
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Cui, Li, Gao, Yuan et al., Teicoplanin inhibits Ebola pseudovirus infection in cell culture, Antivir. Res
Zaki, Van, Bestebroer, Osterhaus, Fouchier, Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia, N. Engl. J. Med
Zhu, Zhang, Wang, Li, Yang et al., A novel coronavirus from patients with pneumonia in China, 2019, N. Engl. J. Med
{ 'indexed': {'date-parts': [[2024, 5, 10]], 'date-time': '2024-05-10T06:33:05Z', 'timestamp': 1715322785370},
'reference-count': 39,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2021, 4, 27]],
'date-time': '2021-04-27T00:00:00Z',
'timestamp': 1619481600000},
'content-version': 'am',
'delay-in-days': 269,
'URL': 'http://www.elsevier.com/open-access/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'stm-asf',
'delay-in-days': 0,
'URL': 'https://doi.org/10.15223/policy-017'},
{ 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'stm-asf',
'delay-in-days': 0,
'URL': 'https://doi.org/10.15223/policy-037'},
{ 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'stm-asf',
'delay-in-days': 0,
'URL': 'https://doi.org/10.15223/policy-012'},
{ 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'stm-asf',
'delay-in-days': 0,
'URL': 'https://doi.org/10.15223/policy-029'},
{ 'start': { 'date-parts': [[2020, 8, 1]],
'date-time': '2020-08-01T00:00:00Z',
'timestamp': 1596240000000},
'content-version': 'stm-asf',
'delay-in-days': 0,
'URL': 'https://doi.org/10.15223/policy-004'}],
'funder': [ { 'DOI': '10.13039/501100008530',
'name': 'European Regional Development Fund',
'doi-asserted-by': 'publisher'},
{ 'DOI': '10.13039/501100001665',
'name': 'Agence Nationale de la Recherche',
'doi-asserted-by': 'publisher'}],
'content-domain': {'domain': ['elsevier.com', 'sciencedirect.com'], 'crossmark-restriction': True},
'published-print': {'date-parts': [[2020, 8]]},
'DOI': '10.1016/j.micpath.2020.104228',
'type': 'journal-article',
'created': {'date-parts': [[2020, 4, 25]], 'date-time': '2020-04-25T06:33:13Z', 'timestamp': 1587796393000},
'page': '104228',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 222,
'title': 'In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic '
'effect',
'prefix': '10.1016',
'volume': '145',
'author': [ {'given': 'Julien', 'family': 'Andreani', 'sequence': 'first', 'affiliation': []},
{'given': 'Marion', 'family': 'Le Bideau', 'sequence': 'additional', 'affiliation': []},
{'given': 'Isabelle', 'family': 'Duflot', 'sequence': 'additional', 'affiliation': []},
{'given': 'Priscilla', 'family': 'Jardot', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-2058-1696',
'authenticated-orcid': False,
'given': 'Clara',
'family': 'Rolland',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-7740-0518',
'authenticated-orcid': False,
'given': 'Manon',
'family': 'Boxberger',
'sequence': 'additional',
'affiliation': []},
{'given': 'Nathalie', 'family': 'Wurtz', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jean-Marc', 'family': 'Rolain', 'sequence': 'additional', 'affiliation': []},
{'given': 'Philippe', 'family': 'Colson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bernard', 'family': 'La Scola', 'sequence': 'additional', 'affiliation': []},
{'given': 'Didier', 'family': 'Raoult', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'issue': '8',
'key': '10.1016/j.micpath.2020.104228_bib1',
'doi-asserted-by': 'crossref',
'first-page': '727',
'DOI': '10.1056/NEJMoa2001017',
'article-title': 'A novel coronavirus from patients with pneumonia in China, 2019',
'volume': '382',
'author': 'Zhu',
'year': '2020',
'journal-title': 'N. Engl. J. Med.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib2',
'doi-asserted-by': 'crossref',
'DOI': '10.1056/NEJMoa2002032',
'article-title': 'Clinical characteristics of coronavirus disease 2019 in China',
'author': 'Guan',
'year': '2020',
'journal-title': 'N. Engl. J. Med.'},
{ 'issue': '10',
'key': '10.1016/j.micpath.2020.104228_bib3',
'doi-asserted-by': 'crossref',
'first-page': '970',
'DOI': '10.1056/NEJMc2001468',
'article-title': 'Transmission of 2019-nCoV infection from an asymptomatic contact in '
'Germany',
'volume': '382',
'author': 'Rothe',
'year': '2020',
'journal-title': 'N. Engl. J. Med.'},
{ 'issue': '19',
'key': '10.1016/j.micpath.2020.104228_bib4',
'doi-asserted-by': 'crossref',
'first-page': '1814',
'DOI': '10.1056/NEJMoa1211721',
'article-title': 'Isolation of a novel coronavirus from a man with pneumonia in Saudi '
'Arabia',
'volume': '367',
'author': 'Zaki',
'year': '2012',
'journal-title': 'N. Engl. J. Med.'},
{ 'issue': '4',
'key': '10.1016/j.micpath.2020.104228_bib5',
'doi-asserted-by': 'crossref',
'first-page': '176',
'DOI': '10.1111/j.1440-1754.2007.01246.x',
'article-title': 'Human (non-severe acute respiratory syndrome) coronavirus infections in '
'hospitalised children in France',
'volume': '44',
'author': 'Vabret',
'year': '2008',
'journal-title': 'J. Paediatr. Child Health'},
{ 'issue': '7',
'key': '10.1016/j.micpath.2020.104228_bib6',
'doi-asserted-by': 'crossref',
'first-page': '1018',
'DOI': '10.1086/644537',
'article-title': 'What is a pandemic?',
'volume': '200',
'author': 'Morens',
'year': '2009',
'journal-title': 'J. Infect. Dis.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib7',
'doi-asserted-by': 'crossref',
'first-page': '72',
'DOI': '10.12688/f1000research.22211.2',
'article-title': 'Therapeutic strategies in an outbreak scenario to treat the novel '
'coronavirus originating in Wuhan, China',
'volume': '9',
'author': 'Kruse',
'year': '2020',
'journal-title': 'F1000Res'},
{ 'issue': '3',
'key': '10.1016/j.micpath.2020.104228_bib8',
'doi-asserted-by': 'crossref',
'first-page': '105924',
'DOI': '10.1016/j.ijantimicag.2020.105924',
'article-title': 'Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and '
'coronavirus disease-2019 (COVID-19): the epidemic and the challenges',
'volume': '55',
'author': 'Lai',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'key': '10.1016/j.micpath.2020.104228_bib9',
'doi-asserted-by': 'crossref',
'first-page': '105932',
'DOI': '10.1016/j.ijantimicag.2020.105932',
'article-title': 'Chloroquine and hydroxychloroquine as available weapons to fight '
'COVID-19',
'author': 'Colson',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'key': '10.1016/j.micpath.2020.104228_bib10',
'doi-asserted-by': 'crossref',
'first-page': '3327',
'DOI': '10.1073/pnas.75.7.3327',
'article-title': 'Fluorescence probe measurement of the intralysosomal pH in living cells '
'and the perturbation of pH various agents',
'volume': '75',
'author': 'Ohkuma',
'year': '1978',
'journal-title': 'Proc. Natl. Acad. Sci. U.S.A.'},
{ 'issue': '8',
'key': '10.1016/j.micpath.2020.104228_bib11',
'doi-asserted-by': 'crossref',
'first-page': '3416',
'DOI': '10.1128/AAC.01509-08',
'article-title': 'Antiviral activity of chloroquine against human coronavirus OC43 '
'infection in newborn mice',
'volume': '53',
'author': 'Keyaerts',
'year': '2009',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib12',
'doi-asserted-by': 'crossref',
'first-page': '69',
'DOI': '10.1186/1743-422X-2-69',
'article-title': 'Chloroquine is a potent inhibitor of SARS coronavirus infection and '
'spread',
'volume': '2',
'author': 'Vincent',
'year': '2005',
'journal-title': 'Virol. J.'},
{ 'issue': '11',
'key': '10.1016/j.micpath.2020.104228_bib13',
'doi-asserted-by': 'crossref',
'first-page': '722',
'DOI': '10.1016/S1473-3099(03)00806-5',
'article-title': "Effects of chloroquine on viral infections: an old drug against today's "
'diseases?',
'volume': '3',
'author': 'Savarino',
'year': '2003',
'journal-title': 'Lancet Infect. Dis.'},
{ 'issue': '8',
'key': '10.1016/j.micpath.2020.104228_bib14',
'doi-asserted-by': 'crossref',
'first-page': '4875',
'DOI': '10.1128/AAC.03011-14',
'article-title': 'Screening of an FDA-approved compound library identifies four '
'small-molecule inhibitors of Middle East respiratory syndrome '
'coronavirus replication in cell culture',
'volume': '58',
'author': 'de Wilde',
'year': '2014',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'issue': '2',
'key': '10.1016/j.micpath.2020.104228_bib15',
'doi-asserted-by': 'crossref',
'first-page': '150',
'DOI': '10.1016/j.antiviral.2007.10.011',
'article-title': 'Inhibition of human coronavirus 229E infection in human epithelial lung '
'cells (L132) by chloroquine: involvement of p38 MAPK and ERK',
'volume': '77',
'author': 'Kono',
'year': '2008',
'journal-title': 'Antivir. Res.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib16',
'doi-asserted-by': 'crossref',
'first-page': '105938',
'DOI': '10.1016/j.ijantimicag.2020.105938',
'article-title': 'New insights on the antiviral effects of chloroquine against '
'coronavirus: what to expect for COVID-19?',
'author': 'Devaux',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'issue': '1',
'key': '10.1016/j.micpath.2020.104228_bib17',
'doi-asserted-by': 'crossref',
'first-page': '264',
'DOI': '10.1016/j.bbrc.2004.08.085',
'article-title': 'In vitro inhibition of severe acute respiratory syndrome coronavirus by '
'chloroquine',
'volume': '323',
'author': 'Keyaerts',
'year': '2004',
'journal-title': 'Biochem. Biophys. Res. Commun.'},
{ 'issue': '3',
'key': '10.1016/j.micpath.2020.104228_bib18',
'doi-asserted-by': 'crossref',
'first-page': '269',
'DOI': '10.1038/s41422-020-0282-0',
'article-title': 'Remdesivir and chloroquine effectively inhibit the recently emerged '
'novel coronavirus (2019-nCoV) in vitro',
'volume': '30',
'author': 'Wang',
'year': '2020',
'journal-title': 'Cell Res.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib19',
'doi-asserted-by': 'crossref',
'first-page': '16',
'DOI': '10.1038/s41421-020-0156-0',
'article-title': 'Hydroxychloroquine, a less toxic derivative of chloroquine, is '
'effective in inhibiting SARS-CoV-2 infection in vitro',
'volume': '6',
'author': 'Liu',
'year': '2020',
'journal-title': 'Cell Discov.'},
{ 'issue': '2',
'key': '10.1016/j.micpath.2020.104228_bib20',
'doi-asserted-by': 'crossref',
'first-page': '167',
'DOI': '10.1001/archinte.159.2.167',
'article-title': 'Treatment of Q fever endocarditis : comparison of two regimens '
'containing doxycycline and ofloxacin or hydroxychloroquine',
'volume': '159',
'author': 'Raoult',
'year': '1999',
'journal-title': 'Arch. Intern. Med.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib21',
'doi-asserted-by': 'crossref',
'first-page': '1512',
'DOI': '10.1128/AAC.34.8.1512',
'article-title': 'Bactericidal effect of Doxycycline associated with lysosomotropic '
'agents on Coxiella burnetii in P388D1 cells',
'volume': '34',
'author': 'Raoult',
'year': '1990',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'issue': '3',
'key': '10.1016/j.micpath.2020.104228_bib22',
'doi-asserted-by': 'crossref',
'first-page': '747',
'DOI': '10.1128/AAC.48.3.747-752.2004',
'article-title': 'Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells',
'volume': '48',
'author': 'Boulos',
'year': '2004',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'issue': '1',
'key': '10.1016/j.micpath.2020.104228_bib23',
'doi-asserted-by': 'crossref',
'first-page': '55',
'DOI': '10.1056/NEJMra062477',
'article-title': "Whipple's disease",
'volume': '356',
'author': 'Fenollar',
'year': '2007',
'journal-title': 'N. Engl. J. Med.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib24',
'doi-asserted-by': 'crossref',
'first-page': '166',
'DOI': '10.1016/j.jchromb.2017.06.011',
'article-title': 'Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and '
'doxycycline from serum samples for the therapeutic drug monitoring of Q '
"fever and Whipple's disease",
'volume': '1060',
'author': 'Armstrong',
'year': '2017',
'journal-title': 'J. Chromatogr. B Analyt Technol. Biomed. Life Sci.'},
{ 'issue': '1',
'key': '10.1016/j.micpath.2020.104228_bib25',
'doi-asserted-by': 'crossref',
'first-page': '72',
'DOI': '10.5582/bst.2020.01047',
'article-title': 'Breakthrough: chloroquine phosphate has shown apparent efficacy in '
'treatment of COVID-19 associated pneumonia in clinical studies',
'volume': '14',
'author': 'Gao',
'year': '2020',
'journal-title': 'Biosci. Trends'},
{ 'key': '10.1016/j.micpath.2020.104228_bib26',
'doi-asserted-by': 'crossref',
'first-page': '1',
'DOI': '10.1016/j.antiviral.2015.11.003',
'article-title': 'Teicoplanin inhibits Ebola pseudovirus infection in cell culture',
'volume': '125',
'author': 'Wang',
'year': '2016',
'journal-title': 'Antivir. Res.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib27',
'article-title': 'Teicoplanin potently blocks the cell entry of 2019-nCoV',
'author': 'Zhang',
'year': '2020',
'journal-title': 'bioRxiv'},
{ 'issue': '50',
'key': '10.1016/j.micpath.2020.104228_bib28',
'doi-asserted-by': 'crossref',
'first-page': '14408',
'DOI': '10.1073/pnas.1618029113',
'article-title': 'Zika virus cell tropism in the developing human brain and inhibition by '
'azithromycin',
'volume': '113',
'author': 'Retallack',
'year': '2016',
'journal-title': 'Proc. Natl. Acad. Sci. U. S. A.'},
{ 'issue': '1',
'key': '10.1016/j.micpath.2020.104228_bib29',
'doi-asserted-by': 'crossref',
'first-page': '6',
'DOI': '10.4172/1948-5964.1000173',
'article-title': 'Azithromycin inhibits the replication of Zika virus',
'volume': '10',
'author': 'Bosseboeuf',
'year': '2018',
'journal-title': 'J. Antivir. Antiretrovir.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib30',
'doi-asserted-by': 'crossref',
'DOI': '10.1128/AAC.00394-19',
'article-title': 'Azithromycin protects against Zika virus infection by upregulating '
'virus-induced type I and III interferon responses',
'author': 'Li',
'year': '2019',
'journal-title': 'Antimicrob. Agents Chemother.'},
{ 'issue': '1',
'key': '10.1016/j.micpath.2020.104228_bib31',
'doi-asserted-by': 'crossref',
'first-page': '52',
'DOI': '10.1097/INF.0000000000001708',
'article-title': 'Variations in antibiotic and azithromycin prescribing for children by '
'geography and specialty-United States, 2013',
'volume': '37',
'author': 'Fleming-Dutra',
'year': '2018',
'journal-title': 'Pediatr. Infect. Dis. J.'},
{ 'key': '10.1016/j.micpath.2020.104228_bib32',
'series-title': 'Focusing on the unfolded protein response and autophagy related pathways '
'to reposition common approved drugs against COVID-19',
'author': 'Nabirothckin',
'year': '2020'},
{ 'key': '10.1016/j.micpath.2020.104228_bib33',
'doi-asserted-by': 'crossref',
'first-page': '105949',
'DOI': '10.1016/j.ijantimicag.2020.105949',
'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results '
'of an open-label non-randomized clinical trial',
'author': 'Gautret',
'year': '2020',
'journal-title': 'Int. J. Antimicrob. Agents'},
{ 'key': '10.1016/j.micpath.2020.104228_bib34',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.tmaid.2020.101632',
'article-title': 'Rapid viral diagnosis and ambulatory management of suspected COVID-19 '
'cases presenting at the infections diseases referral hospital in '
'Marseille, France, -January 31st to March 1st, 2020: a respiratory '
'virus snapshot',
'author': 'Amrane',
'year': '2020',
'journal-title': 'Trav. Med. Infect. Dis.'},
{ 'issue': '4',
'key': '10.1016/j.micpath.2020.104228_bib35',
'doi-asserted-by': 'crossref',
'first-page': '402',
'DOI': '10.1006/meth.2001.1262',
'article-title': 'Analysis of relative gene expression data using real-time quantitative '
'PCR and the 2(-Delta Delta C(T)) Method',
'volume': '25',
'author': 'Livak',
'year': '2001',
'journal-title': 'Methods'},
{ 'key': '10.1016/j.micpath.2020.104228_bib36',
'doi-asserted-by': 'crossref',
'first-page': '27',
'DOI': '10.1016/j.virol.2018.07.025',
'article-title': 'HaCaT epithelial cells as an innovative novel model of rhinovirus '
'infection and impact of clarithromycin treatment on infection kinetics',
'volume': '523',
'author': 'Morgene',
'year': '2018',
'journal-title': 'Virology'},
{ 'issue': '10',
'key': '10.1016/j.micpath.2020.104228_bib37',
'article-title': 'The non-antibiotic macrolide EM900 inhibits rhinovirus infection and '
'cytokine production in human airway epithelial cells',
'volume': '3',
'author': 'Lusamba',
'year': '2015',
'journal-title': 'Physiol Rep'},
{ 'issue': '10',
'key': '10.1016/j.micpath.2020.104228_bib38',
'article-title': 'The non-antibiotic macrolide EM900 inhibits rhinovirus infection and '
'cytokine production in human airway epithelial cells',
'volume': '3',
'author': 'Lusamba',
'year': '2015',
'journal-title': 'Physiol Rep'},
{ 'issue': '3',
'key': '10.1016/j.micpath.2020.104228_bib39',
'doi-asserted-by': 'crossref',
'first-page': '1289',
'DOI': '10.1128/JVI.01281-09',
'article-title': 'Cellular immune responses to severe acute respiratory syndrome '
'coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells '
'are important in control of SARS-CoV infection',
'volume': '84',
'author': 'Chen',
'year': '2010',
'journal-title': 'J Virol'}],
'container-title': 'Microbial Pathogenesis',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0882401020305155?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S0882401020305155?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2023, 3, 5]],
'date-time': '2023-03-05T00:08:30Z',
'timestamp': 1677974910000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S0882401020305155'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 8]]},
'references-count': 39,
'alternative-id': ['S0882401020305155'],
'URL': 'http://dx.doi.org/10.1016/j.micpath.2020.104228',
'relation': {},
'ISSN': ['0882-4010'],
'subject': [],
'container-title-short': 'Microbial Pathogenesis',
'published': {'date-parts': [[2020, 8]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 '
'shows synergistic effect',
'name': 'articletitle',
'label': 'Article Title'},
{'value': 'Microbial Pathogenesis', 'name': 'journaltitle', 'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.micpath.2020.104228',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{'value': '© 2021 Published by Elsevier Ltd.', 'name': 'copyright', 'label': 'Copyright'}],
'article-number': '104228'}
