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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?</title><author><name sortKey="Baron, Sophie Alexandra" sort="Baron, Sophie Alexandra" uniqKey="Baron S" first="Sophie Alexandra" last="Baron">Sophie Alexandra Baron</name><affiliation><nlm:aff id="aff0001">Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation></author><author><name sortKey="Devaux, Christian" sort="Devaux, Christian" uniqKey="Devaux C" first="Christian" last="Devaux">Christian Devaux</name><affiliation><nlm:aff id="aff0002">Aix Marseille Univ, IRD, APHM, VITROME, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation></author><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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, 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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0003">IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, 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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0003">IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32179150</idno><idno type="pmc">7102624</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102624</idno><idno type="RBID">PMC:7102624</idno><idno type="doi">10.1016/j.ijantimicag.2020.105944</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000D32</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D32</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?</title><author><name sortKey="Baron, Sophie Alexandra" sort="Baron, Sophie Alexandra" uniqKey="Baron S" first="Sophie Alexandra" last="Baron">Sophie Alexandra Baron</name><affiliation><nlm:aff id="aff0001">Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation></author><author><name sortKey="Devaux, Christian" sort="Devaux, Christian" uniqKey="Devaux C" first="Christian" last="Devaux">Christian Devaux</name><affiliation><nlm:aff id="aff0002">Aix Marseille Univ, IRD, APHM, VITROME, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation></author><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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, 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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0003">IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, 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 Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff0003">IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, 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><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="celist0001"><list-item id="celistitem0001"><label>•</label><p id="para0001">A new coronavirus, SARS-CoV-2, has emerged from China and is spreading worldwide</p></list-item><list-item id="celistitem0002"><label>•</label><p id="para0002">Due to the lack of specific treatment, we suggest the use of drug repurposing</p></list-item><list-item id="celistitem0003"><label>•</label><p id="para0003">Teicoplanin, an antibiotic, has already shown activity against previous coronavirus.</p></list-item><list-item id="celistitem0004"><label>•</label><p id="para0004">Its activity seems conserved in vitro against this new coronavirus.</p></list-item><list-item id="celistitem0005"><label>•</label><p id="para0005">Further works are needed to confirm its activity in vivo</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N Zhu</name></author><author><name sortKey="Zhang, D" uniqKey="Zhang D">D Zhang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Yang, B" uniqKey="Yang B">B Yang</name></author><author><name sortKey="Song, J" uniqKey="Song J">J Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, C C" uniqKey="Lai C">C-C Lai</name></author><author><name sortKey="Shih, T P" uniqKey="Shih T">T-P Shih</name></author><author><name sortKey="Ko, W C" uniqKey="Ko W">W-C Ko</name></author><author><name sortKey="Tang, H J" uniqKey="Tang H">H-J Tang</name></author><author><name sortKey="Hsueh, P R" uniqKey="Hsueh P">P-R Hsueh</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Cao, R" uniqKey="Cao R">R Cao</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Xu, M" uniqKey="Xu M">M Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Colson, P" uniqKey="Colson P">P Colson</name></author><author><name sortKey="Rolain, J M" uniqKey="Rolain J">J-M Rolain</name></author><author><name sortKey="Raoult, D" uniqKey="Raoult D">D Raoult</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ko, W C" uniqKey="Ko W">W-C Ko</name></author><author><name sortKey="Rolain, J M" uniqKey="Rolain J">J-M Rolain</name></author><author><name sortKey="Lee, N Y" uniqKey="Lee N">N-Y Lee</name></author><author><name sortKey="Chen, P L" uniqKey="Chen P">P-L Chen</name></author><author><name sortKey="Huang, C T" uniqKey="Huang C">C-T Huang</name></author><author><name sortKey="Lee, P I" uniqKey="Lee P">P-I Lee</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, N" uniqKey="Zhou N">N Zhou</name></author><author><name sortKey="Pan, T" uniqKey="Pan T">T Pan</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q Li</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Bai, C" uniqKey="Bai C">C Bai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Colson, P" uniqKey="Colson P">P Colson</name></author><author><name sortKey="Raoult, D" uniqKey="Raoult D">D. Raoult</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<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>Elsevier Science Publishers</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32179150</article-id><article-id pub-id-type="pmc">7102624</article-id><article-id pub-id-type="publisher-id">S0924-8579(20)30094-7</article-id><article-id pub-id-type="doi">10.1016/j.ijantimicag.2020.105944</article-id><article-id pub-id-type="publisher-id">105944</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0001"><name><surname>Baron</surname><given-names>Sophie Alexandra</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0002"><name><surname>Devaux</surname><given-names>Christian</given-names></name><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0003"><name><surname>Colson</surname><given-names>Philippe</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0004"><name><surname>Raoult</surname><given-names>Didier</given-names></name><xref rid="aff0001" ref-type="aff">a</xref><xref rid="aff0003" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au0005"><name><surname>Rolain</surname><given-names>Jean-Marc</given-names></name><email>jean-marc.rolain@univ-amu.fr</email><xref rid="aff0001" ref-type="aff">a</xref><xref rid="aff0003" ref-type="aff">c</xref><xref rid="cor0001" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="aff0001"><label>a</label>Aix Marseille Univ, IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</aff><aff id="aff0002"><label>b</label>Aix Marseille Univ, IRD, APHM, VITROME, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</aff><aff id="aff0003"><label>c</label>IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France</aff><author-notes><corresp id="cor0001"><label>⁎</label>Corresponding author: Jean-Marc Rolain, Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, Faculté de Médecine et de Pharmacie, 19-21 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France. Tel.: (33) 4 13 73 24 01 <email>jean-marc.rolain@univ-amu.fr</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>13</day><month>3</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="epub"><day>13</day><month>3</month><year>2020</year></pub-date><elocation-id>105944</elocation-id><permissions><copyright-statement>© 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.</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><abstract abstract-type="author-highlights" id="abs0001"><title>Highlights</title><p><list list-type="simple" id="celist0001"><list-item id="celistitem0001"><label>•</label><p id="para0001">A new coronavirus, SARS-CoV-2, has emerged from China and is spreading worldwide</p></list-item><list-item id="celistitem0002"><label>•</label><p id="para0002">Due to the lack of specific treatment, we suggest the use of drug repurposing</p></list-item><list-item id="celistitem0003"><label>•</label><p id="para0003">Teicoplanin, an antibiotic, has already shown activity against previous coronavirus.</p></list-item><list-item id="celistitem0004"><label>•</label><p id="para0004">Its activity seems conserved in vitro against this new coronavirus.</p></list-item><list-item id="celistitem0005"><label>•</label><p id="para0005">Further works are needed to confirm its activity in vivo</p></list-item></list></p></abstract><abstract id="abs0002"><p>In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.</p></abstract><kwd-group id="keys0001"><title>Keywords</title><kwd>SARS-CoV-2</kwd><kwd>Drug repurposing</kwd><kwd>Teicoplanin</kwd><kwd>COVID-19</kwd></kwd-group></article-meta></front><body><sec id="sec0001"><title>Hot topic</title><p id="para0006">In December 2019, a new coronavirus has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency [<xref rid="bib0001" ref-type="bibr">1</xref>,<xref rid="bib0002" ref-type="bibr">2</xref>]. This coronavirus, named SARS-CoV-2 (formerly 2019-nCoV), is responsible for respiratory infections including pneumonia with a mortality rate estimated about 2%-2.5%, increasing with age and the existence of underlying diseases. On the first days of March 2020, an estimated 89,068 cases had been confirmed worldwide by WHO (a number likely underestimated due to the existence of asymptomatic carriers) and the epidemic has already left 3,046 dead from COVID-19 disease, the majority of them occurring in China. Because COVID-19 is now becoming pandemic and in the absence of known validated efficient therapy, efforts of laboratories and medical teams have focused on repurposing FDA-approved drugs to treat the most severe cases of infection. Drug repurposing is an effective way to quickly identify therapeutic drug with a known safety profile to treat an emerging disease. Chloroquine/hydroxychloroquine, a front-line drug used in the treatment and prophylaxis of malaria also used in autoimmune disease had been shown to inhibit the replication of several DNA and RNA viruses, including most of human coronaviruses <xref rid="bib0003" ref-type="bibr">[3]</xref>. Recently, chloroquine was found to inhibit SARS-CoV-2 <italic>in vitro</italic> and its hydroxylated form has been proposed as a possible therapy to treat patients infected with SARS-CoV-2 [<xref rid="bib0004" ref-type="bibr">4</xref>,<xref rid="bib0005" ref-type="bibr">5</xref>]. In this contest, other drug showed significant efficacy against SARS-Cov-2 <italic>in vitro</italic> such as remdesivir, lopinavir, ribavirin or ritonavir (<ext-link ext-link-type="uri" xlink:href="https://drugvirus.info/" id="interref0001">https://drugvirus.info/</ext-link>) <xref rid="bib0006" ref-type="bibr">[6]</xref>.</p><p id="para0007">Teicoplanin, a glycopeptide antibiotic routinely used to treat bacterial infection was found to be active <italic>in vitro</italic> against SARS-CoV, has joined the list of molecules that could be used as therapeutic arsenal against COVID-19 <xref rid="bib0007" ref-type="bibr">[7]</xref>. This antibiotic, currently used in the treatment of Gram-positive bacterial infection, especially in Staphylococcal infections, has already showed efficacy against various viruses such as Ebola, influenza virus, flavivirus, hepatitis C virus, HIV virus and on coronavirus such as MERS-CoV and SARS-CoV [<xref rid="bib0008" ref-type="bibr">8</xref>,<xref rid="bib0009" ref-type="bibr">9</xref>]. A patent was filed for the treatment of infection caused by MERS-CoV in 2016 <xref rid="bib0010" ref-type="bibr">[10]</xref>. According to Zhou and colleagues, in coronaviruses, teicoplanin acts on the early step of the viral life cycle by inhibiting the low pH cleavage of the viral spike protein by cathepsin L in the late endosomes thereby preventing the release of genomic viral RNA and the continuation of virus replication cycle. A recent study by the same authors showed that this activity was conserved on SARS-Cov-2 (the target sequence that serve as cleavage site for cathepsin L is conserved among SARS-CoV spike protein) <xref rid="bib0007" ref-type="bibr">[7]</xref>. The concentration of teicoplanin required to inhibit 50% of viruses (IC<sub>50</sub>) <italic>in vitro</italic> was 1.66 µM, which is much lower than the concentration reached in human blood (8.78 µM for a daily dose of 400 mg) <xref rid="bib0007" ref-type="bibr">[7]</xref>. These preliminary results need to be confirmed now by a randomized clinical trial.</p><p id="para0008">Based on our experience of teicoplanin usage in the treatment of infectious diseases, we encourage further investigation of the antiviral effect of this molecule on SARS-CoV-2 and suggest teicoplanin as another potential alternative for the treatment of COVID-19 disease.</p></sec><sec sec-type="COI-statement"><title>Declaration of Competing Interests</title><p id="para0011">The authors declare that they have no competing interests.</p></sec></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>Zhu</surname><given-names>N</given-names></name><name><surname>Zhang</surname><given-names>D</given-names></name><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Yang</surname><given-names>B</given-names></name><name><surname>Song</surname><given-names>J</given-names></name></person-group><article-title>A Novel Coronavirus from Patients with Pneumonia in China, 2019</article-title><source>N Engl J Med</source><volume>382</volume><year>2020</year><fpage>727</fpage><lpage>733</lpage><comment>https://doi.org/</comment><pub-id pub-id-type="pmid">31978945</pub-id></element-citation></ref><ref id="bib0002"><label>2</label><element-citation publication-type="journal" id="sbref0002"><person-group person-group-type="author"><name><surname>Lai</surname><given-names>C-C</given-names></name><name><surname>Shih</surname><given-names>T-P</given-names></name><name><surname>Ko</surname><given-names>W-C</given-names></name><name><surname>Tang</surname><given-names>H-J</given-names></name><name><surname>Hsueh</surname><given-names>P-R</given-names></name></person-group><article-title>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges</article-title><source>Int J Antimicrob Agents</source><year>2020</year><object-id pub-id-type="publisher-id">105924</object-id><comment>https://doi.org/10.1016/j.ijantimicag.2020.105924</comment></element-citation></ref><ref id="bib0003"><label>3</label><mixed-citation publication-type="other" id="othref0001">Devaux C, Rolain J-M, Colson P, Raoult D. 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USE OF TEICOPLANIN ANTI-MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS. WO/2016/201692, 2015.</mixed-citation></ref></ref-list><ack id="ack0001"><sec id="sec0002"><title>Funding</title><p id="para0009">This work was supported by the French Government under the « Investissements d'avenir » (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research), (reference: Méditerranée Infection 10-IAHU-03). This work was supported by Région Provence Alpes Côte d'Azur and European funding FEDER PRIMI.</p></sec><sec id="sec0003"><title>Ethical Approval</title><p id="para0010">Not required</p></sec></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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