Chloroquine for the 2019 novel coronavirus SARS-CoV-2
Identifieur interne : 000A37 ( Pmc/Corpus ); précédent : 000A36; suivant : 000A38Chloroquine for the 2019 novel coronavirus SARS-CoV-2
Auteurs : Philippe Colson ; Jean-Marc Rolain ; Didier RaoultSource :
- International Journal of Antimicrobial Agents [ 0924-8579 ] ; 2020.
Url:
DOI: 10.1016/j.ijantimicag.2020.105923
PubMed: 32070753
PubMed Central: 7134866
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Chloroquine for the 2019 novel coronavirus SARS-CoV-2</title><author><name sortKey="Colson, Philippe" sort="Colson, Philippe" uniqKey="Colson P" first="Philippe" last="Colson">Philippe Colson</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32070753</idno><idno type="pmc">7134866</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134866</idno><idno type="RBID">PMC:7134866</idno><idno type="doi">10.1016/j.ijantimicag.2020.105923</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000A37</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A37</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Chloroquine for the 2019 novel coronavirus SARS-CoV-2</title><author><name sortKey="Colson, Philippe" sort="Colson, Philippe" uniqKey="Colson P" first="Philippe" last="Colson">Philippe Colson</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation><nlm:aff id="aff0001">Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0002">IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Antimicrobial Agents</title><idno type="ISSN">0924-8579</idno><idno type="eISSN">1872-7913</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mullard, A" uniqKey="Mullard A">A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Antimicrob Agents</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Antimicrob. Agents</journal-id><journal-title-group><journal-title>International Journal of Antimicrobial Agents</journal-title></journal-title-group><issn pub-type="ppub">0924-8579</issn><issn pub-type="epub">1872-7913</issn><publisher><publisher-name>Published by Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32070753</article-id><article-id pub-id-type="pmc">7134866</article-id><article-id pub-id-type="publisher-id">S0924-8579(20)30066-2</article-id><article-id pub-id-type="doi">10.1016/j.ijantimicag.2020.105923</article-id><article-id pub-id-type="publisher-id">105923</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Chloroquine for the 2019 novel coronavirus SARS-CoV-2</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0001"><name><surname>Colson</surname><given-names>Philippe</given-names></name><xref rid="aff0001" ref-type="aff">a</xref><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0002"><name><surname>Rolain</surname><given-names>Jean-Marc</given-names></name><xref rid="aff0001" ref-type="aff">a</xref><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0003"><name><surname>Raoult</surname><given-names>Didier</given-names></name><email>didier.raoult@gmail.com</email><xref rid="aff0001" ref-type="aff">a</xref><xref rid="aff0002" ref-type="aff">b</xref><xref rid="cor0001" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="aff0001"><label>a</label>Aix-Marseille Université, Institut de Recherche pour le Développement (IRD), Assistance Publique–Hôpitaux de Marseille (AP-HM), MEPHI, 27 boulevard Jean Moulin, 13005 Marseille, France</aff><aff id="aff0002"><label>b</label>IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France</aff><author-notes><corresp id="cor0001"><label>⁎</label>Corresponding author. Present address: IHU Méditerranée Infection, 19–21 boulevard Jean Moulin, 13005 Marseille, France. Tel.: +33 4 13 732 401; fax: +33 4 13 732 402. <email>didier.raoult@gmail.com</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>15</day><month>2</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>3</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>15</day><month>2</month><year>2020</year></pub-date><volume>55</volume><issue>3</issue><fpage>105923</fpage><lpage>105923</lpage><history><date date-type="received"><day>11</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>11</day><month>2</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Published by Elsevier B.V.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></article-meta></front><body><p id="para0001">A movement to reposition drugs has been initiated in recent years <xref rid="bib0001" ref-type="bibr">[1]</xref>. In this strategy, it is important to use drugs that have been proven to be harmless and whose pharmacokinetics and optimal dosage are well known. In the current episode of novel coronavirus (SARS-CoV-2) emergence <xref rid="bib0002" ref-type="bibr">[2]</xref>, we find a spectacular example of possible repositioning of drugs, particularly chloroquine. We had 20 years ago proposed to systematically test chloroquine in viral infections because it had been shown to be effective <italic>in vitro</italic> against a broad range of viruses <xref rid="bib0003" ref-type="bibr">[3</xref>,<xref rid="bib0004" ref-type="bibr">4]</xref>. This drug has multiple activities, one of which is to alkalise the phagolysosome, which hampers the low-pH-dependent steps of viral replication, including fusion and uncoating <xref rid="bib0004" ref-type="bibr">[4]</xref>. Other mechanisms of antiviral activity are poorly explained <xref rid="bib0005" ref-type="bibr">[5]</xref>.</p><p id="para0002">At the time of the severe acute respiratory syndrome (SARS)-associated coronavirus epidemic <xref rid="bib0006" ref-type="bibr">[6]</xref> in 2003, several molecules were tested to assess their effectiveness against this virus. Among these, teicoplanin <xref rid="bib0007" ref-type="bibr">[7]</xref>, an antistaphylococcal agent, had proven efficacy <italic>in vitro</italic>, and this was also the case for chloroquine, at a 50% effective concentration (EC<sub>50</sub>) of approximatively 8 µM, and when added to the cell culture either before of after exposure to the virus <xref rid="bib0005" ref-type="bibr">[5</xref>,<xref rid="bib0008" ref-type="bibr">[8]</xref>, <xref rid="bib0009" ref-type="bibr">[9]</xref>, <xref rid="bib0010" ref-type="bibr">[10]</xref>. These findings ended up being forgotten because of the disappearance of SARS for reasons that are neither clear nor explained <xref rid="bib0011" ref-type="bibr">[11]</xref>. The novel coronavirus currently isolated in China has been, with staggering speed, evaluated regarding its sensitivity to already used drugs <xref rid="bib0012" ref-type="bibr">[12]</xref>. Thus, the new antiviral drug remdesivir <xref rid="bib0013" ref-type="bibr">[13]</xref> as well as chloroquine, at an EC<sub>50</sub> of 1.1 µM, were found to be effective in preventing replication of this virus <xref rid="bib0012" ref-type="bibr">[12]</xref>. Chloroquine is perhaps one of the most prescribed drugs in the world <xref rid="bib0014" ref-type="bibr">[14</xref>,<xref rid="bib0015" ref-type="bibr">15]</xref>. As a matter of fact, all Europeans visiting malaria-endemic geographic areas for decades received chloroquine prophylaxis and continued it for 2 months after their return. In addition, local residents took chloroquine continuously, and treatment of malaria has long been based on this drug. In addition, hydroxychloroquine has been used for decades at much higher doses (up to 600 mg/day) to treat autoimmune diseases <xref rid="bib0016" ref-type="bibr">[16]</xref>. It is difficult to find a product that currently has a better established safety profile than chloroquine. Furthermore, its cost is negligible. Hence, its possible use both in prophylaxis in people exposed to the novel coronavirus and as a curative treatment will probably be promptly evaluated by our Chinese colleagues. If clinical data confirm the biological results, the novel coronavirus-associated disease will have become one of the simplest and cheapest to treat and prevent among infectious respiratory diseases.</p><p id="para0003"><bold>Funding:</bold> This work was supported by the French Government under the ‘Investments for the Future’ program managed by the National Agency for Research (ANR) [Méditerranée-Infection 10-IAHU-03]. The funding sources had no role in the preparation, review or approval of the manuscript.</p><p id="para0004"><bold>Competing interests:</bold> None declared.</p><p id="para0005"><bold>Ethical approval:</bold> Not required.</p></body><back><ref-list id="cebibl1"><title>References</title><ref id="bib0001"><label>1</label><element-citation publication-type="journal" id="sbref0001"><person-group person-group-type="author"><name><surname>Mullard</surname><given-names>A.</given-names></name></person-group><article-title>Drug repurposing programmes get lift off</article-title><source>Nat Rev Drug Discov</source><volume>11</volume><year>2012</year><fpage>505</fpage><lpage>506</lpage><pub-id pub-id-type="pmid">22743966</pub-id></element-citation></ref><ref id="bib0002"><label>2</label><element-citation publication-type="journal" id="sbref0002"><person-group 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