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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">DPP4-directed therapeutic strategies for MERS-CoV</title><author><name sortKey="Reinhold, Dirk" sort="Reinhold, Dirk" uniqKey="Reinhold D" first="Dirk" last="Reinhold">Dirk Reinhold</name><affiliation><nlm:aff id="aff1">Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Brocke, Stefan" sort="Brocke, Stefan" uniqKey="Brocke S" first="Stefan" last="Brocke">Stefan Brocke</name><affiliation><nlm:aff id="aff2">Department of Immunology, Center of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24457167</idno><idno type="pmc">7128741</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128741</idno><idno type="RBID">PMC:7128741</idno><idno type="doi">10.1016/S1473-3099(13)70696-0</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000881</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000881</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">DPP4-directed therapeutic strategies for MERS-CoV</title><author><name sortKey="Reinhold, Dirk" sort="Reinhold, Dirk" uniqKey="Reinhold D" first="Dirk" last="Reinhold">Dirk Reinhold</name><affiliation><nlm:aff id="aff1">Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Brocke, Stefan" sort="Brocke, Stefan" uniqKey="Brocke S" first="Stefan" last="Brocke">Stefan Brocke</name><affiliation><nlm:aff id="aff2">Department of Immunology, Center of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030, USA</nlm:aff></affiliation></author></analytic><series><title level="j">The Lancet. Infectious Diseases</title><idno type="ISSN">1473-3099</idno><idno type="eISSN">1474-4457</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reinhold, D" uniqKey="Reinhold D">D Reinhold</name></author><author><name sortKey="Bank, U" uniqKey="Bank U">U Bank</name></author><author><name sortKey="Tager, M" uniqKey="Tager M">M Tager</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendieta, L" uniqKey="Mendieta L">L Mendieta</name></author><author><name sortKey="Tarrago, T" uniqKey="Tarrago T">T Tarrago</name></author><author><name sortKey="Giralt, E" uniqKey="Giralt E">E Giralt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carlson, Cm" uniqKey="Carlson C">CM Carlson</name></author><author><name sortKey="Turpin, Ea" uniqKey="Turpin E">EA Turpin</name></author><author><name sortKey="Moser, La" uniqKey="Moser L">LA Moser</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="letter"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Lancet Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Infect Dis</journal-id><journal-title-group><journal-title>The Lancet. Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1473-3099</issn><issn pub-type="epub">1474-4457</issn><publisher><publisher-name>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24457167</article-id><article-id pub-id-type="pmc">7128741</article-id><article-id pub-id-type="publisher-id">S1473-3099(13)70696-0</article-id><article-id pub-id-type="doi">10.1016/S1473-3099(13)70696-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>DPP4-directed therapeutic strategies for MERS-CoV</article-title></title-group><contrib-group><contrib contrib-type="author" id="au10"><name><surname>Reinhold</surname><given-names>Dirk</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au20"><name><surname>Brocke</surname><given-names>Stefan</given-names></name><email>sbrocke@uchc.edu</email><xref rid="aff2" ref-type="aff">b</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany</aff><aff id="aff2"><label>b</label>Department of Immunology, Center of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030, USA</aff><pub-date pub-type="pmc-release"><day>20</day><month>1</month><year>2014</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>2</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>20</day><month>1</month><year>2014</year></pub-date><volume>14</volume><issue>2</issue><fpage>100</fpage><lpage>101</lpage><permissions><copyright-statement>Copyright © 2014 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Elsevier Ltd</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><related-article related-article-type="article-reference" id="d32e201" ext-link-type="doi" xlink:href="10.1016/S1473-3099(13)70154-3"></related-article></article-meta></front><body><p id="para10">Christian Drosten and colleages<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> provided the first complete virological profile of a patient infected with Middle East respiratory syndrome coronavirus (MERS-CoV). Previous study findings have shown that dipeptidyl peptidase 4 (DPP4; also known as CD26) serves as the functional receptor for MERS-CoV.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> In view of the importance of DPP4 in regulating immune responses,<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> inhibitors of DPP4 binding and activity could modulate the pathogenesis of viral infection and serve as potential therapeutics.</p><p id="para20">Targeting of the site between the binding domain on the virus surface and the receptor might provide pharmacological action to suppress MERS-CoV infection. Studies have provided new insights into DPP4 interaction with substrates and inhibitors, and numerous inhibitors with varying selectivity have been characterised in DPP4 binding and functional assays.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Additionally, on the basis of our work on the use of DPP4 inhibitors as a treatment for autoimmune disease, DPP4 inhibition could suppress the damaging aspects of the body's own antiviral immune response by modulating inflammation.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Reversible inhibitors of DPP4 enzymatic activity suppress T-cell proliferation and production of proinflammatory cytokines as well as interleukin 10.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> As we have shown, DPP4 inhibitor-mediated suppression acts partly through the induction of transforming growth factor β 1 (TGFβ1) production by effector T cells. Consistent with this mechanism, we noted a significant increase of TGFβ1 concentrations in tissue and plasma of mice treated with DPP4 inhibitors.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> TGFβ1 induction at the site of inflammation could be an additional therapeutic benefit of DPP4 inhibitor treatment, because TGFβ1 is an essential regulator of immune responses in severe respiratory infections.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Notably, Carlson and colleagues<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> reported that injection of TGFβ1 delayed mortality and reduced viral titres of mice infected with H5N1 influenza virus, whereas neutralisation of TGFβ1 during H5N1 and pandemic 2009 H1N1 infection had opposing effects.</p><p id="para30">As a caveat, a side-effect of DPP4 inhibitor treatment could be suppression of immunity mediated by effector T cells. This action could limit their use in severe infection because it might inhibit the protective antiviral immune response.</p><p id="para40">In sum, it could well be worthwhile to establish the antiviral action of various DPP4 inhibitors through in-vitro and preclinical testing and, depending on the results, cautiously to examine their potential therapeutic effect in severe viral infections, including infection by MERS-CoV.</p></body><back><ref-list id="bibl10"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sbref10"><person-group person-group-type="author"><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Seilmaier</surname><given-names>M</given-names></name><name><surname>Corman</surname><given-names>VM</given-names></name></person-group><article-title>Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection</article-title><source>Lancet Infect Dis</source><volume>13</volume><year>2013</year><fpage>745</fpage><lpage>751</lpage><pub-id pub-id-type="pmid">23782859</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal" id="sbref20"><person-group person-group-type="author"><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Mou</surname><given-names>H</given-names></name><name><surname>Smits</surname><given-names>SL</given-names></name></person-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title><source>Nature</source><volume>495</volume><year>2013</year><fpage>251</fpage><lpage>254</lpage><pub-id pub-id-type="pmid">23486063</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal" id="sbref30"><person-group person-group-type="author"><name><surname>Reinhold</surname><given-names>D</given-names></name><name><surname>Bank</surname><given-names>U</given-names></name><name><surname>Tager</surname><given-names>M</given-names></name></person-group><article-title>DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis</article-title><source>Front Biosci</source><volume>13</volume><year>2008</year><fpage>2356</fpage><lpage>2363</lpage><pub-id pub-id-type="pmid">17981717</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sbref40"><person-group person-group-type="author"><name><surname>Mendieta</surname><given-names>L</given-names></name><name><surname>Tarrago</surname><given-names>T</given-names></name><name><surname>Giralt</surname><given-names>E</given-names></name></person-group><article-title>Recent patents of dipeptidyl peptidase IV inhibitors</article-title><source>Expert Opin Ther Pat</source><volume>21</volume><year>2011</year><fpage>1693</fpage><lpage>1741</lpage><pub-id pub-id-type="pmid">22017411</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sbref50"><person-group person-group-type="author"><name><surname>Carlson</surname><given-names>CM</given-names></name><name><surname>Turpin</surname><given-names>EA</given-names></name><name><surname>Moser</surname><given-names>LA</given-names></name></person-group><article-title>Transforming growth factor-beta: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis</article-title><source>PLoS Pathog</source><volume>6</volume><year>2010</year><fpage>e1001136</fpage><pub-id pub-id-type="pmid">20949074</pub-id></element-citation></ref></ref-list><ack><p>We declare that we have no conflicts of interest.</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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