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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Aminopeptidase N inhibitors and SARS</title><author><name sortKey="Kontoyiannis, Dimitrios P" sort="Kontoyiannis, Dimitrios P" uniqKey="Kontoyiannis D" first="Dimitrios P" last="Kontoyiannis">Dimitrios P. Kontoyiannis</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Pasqualini, Renata" sort="Pasqualini, Renata" uniqKey="Pasqualini R" first="Renata" last="Pasqualini">Renata Pasqualini</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Arap, Wadih" sort="Arap, Wadih" uniqKey="Arap W" first="Wadih" last="Arap">Wadih Arap</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">12737884</idno><idno type="pmc">7135642</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135642</idno><idno type="RBID">PMC:7135642</idno><idno type="doi">10.1016/S0140-6736(03)13186-8</idno><date when="2003">2003</date><idno type="wicri:Area/Pmc/Corpus">000B17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B17</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Aminopeptidase N inhibitors and SARS</title><author><name sortKey="Kontoyiannis, Dimitrios P" sort="Kontoyiannis, Dimitrios P" uniqKey="Kontoyiannis D" first="Dimitrios P" last="Kontoyiannis">Dimitrios P. Kontoyiannis</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Pasqualini, Renata" sort="Pasqualini, Renata" uniqKey="Pasqualini R" first="Renata" last="Pasqualini">Renata Pasqualini</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Arap, Wadih" sort="Arap, Wadih" uniqKey="Arap W" first="Wadih" last="Arap">Wadih Arap</name><affiliation><nlm:aff id="aff1">The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Lancet (London, England)</title><idno type="ISSN">0140-6736</idno><idno type="eISSN">1474-547X</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author><author><name sortKey="Erdman, D" uniqKey="Erdman D">D Erdman</name></author><author><name sortKey="Goldsmith, C" uniqKey="Goldsmith C">C Goldsmith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcintosh, K" uniqKey="Mcintosh K">K McIntosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeager, Cl" uniqKey="Yeager C">CL Yeager</name></author><author><name sortKey="Ashmun, Ra" uniqKey="Ashmun R">RA Ashmun</name></author><author><name sortKey="Williams, Rk" uniqKey="Williams R">RK Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delmas, B" uniqKey="Delmas B">B Delmas</name></author><author><name sortKey="Gelfi, J" uniqKey="Gelfi J">J Gelfi</name></author><author><name sortKey="L Haridon, R" uniqKey="L Haridon R">R L'Haridon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pasqualini, R" uniqKey="Pasqualini R">R Pasqualini</name></author><author><name sortKey="Koivunen, E" uniqKey="Koivunen E">E Koivunen</name></author><author><name sortKey="Kain, R" uniqKey="Kain R">R Kain</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</journal-id><journal-id journal-id-type="iso-abbrev">Lancet</journal-id><journal-title-group><journal-title>Lancet (London, England)</journal-title></journal-title-group><issn pub-type="ppub">0140-6736</issn><issn pub-type="epub">1474-547X</issn><publisher><publisher-name>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">12737884</article-id><article-id pub-id-type="pmc">7135642</article-id><article-id pub-id-type="publisher-id">S0140-6736(03)13186-8</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(03)13186-8</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Aminopeptidase N inhibitors and SARS</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kontoyiannis</surname><given-names>Dimitrios P</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Pasqualini</surname><given-names>Renata</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Arap</surname><given-names>Wadih</given-names></name><email>warap@notes.mdacc.tmc.edu</email><xref rid="aff1" ref-type="aff">a</xref></contrib></contrib-group><aff id="aff1"><label>a</label>The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA</aff><pub-date pub-type="pmc-release"><day>1</day><month>5</month><year>2003</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"><day>3</day><month>5</month><year>2003</year></pub-date><pub-date pub-type="epub"><day>1</day><month>5</month><year>2003</year></pub-date><volume>361</volume><issue>9368</issue><fpage>1558</fpage><lpage>1558</lpage><permissions><copyright-statement>Copyright © 2003 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2003</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></article-meta></front><body><p content-type="salutation">Sir</p><p id="para10">Since initiation of active epidemiological surveillance, the toll of severe acute respiratory syndrome (SARS) has continued to mount. As of April 14, 2003, the cumulative number of cases of SARS was 3169, and 144 deaths have been reported. This epidemic shows no signs of abatement, in part because the mechanism of transmission remains unclear and the agent(s) that causes disease elusive. However, a previously unknown coronavirus, with or without another viral copathogen, has been implicated in the pathogenesis of SARS.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> The involvement of a member of the coronavirus family, a large group of sizeable single-stranded RNA viruses with multiple serotypes, natural hosts, and tissue specificities, is intriguing; these viruses have had a good host adaptation and are frequent causes of the common cold.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> Life-threatening lower respiratory infections caused by coronaviruses are uncommon.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref></p><p id="para20">There are gaps in our understanding of the immunopathogenesis of the respiratory injury caused by these viruses, although it could depend on release of inflammatory mediators.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> No studies have been done on the mechanism of lung injury in coronaviridiae-induced pneumonia, but one would expect similar pathogenic events. Moreover, the antigenic diversity of coronaviridiae capable of causing respiratory infection remains uncertain.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> There are several strains with a tropism to the human respiratory tract.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> Although most of the known strains are related antigenically to the two principal and antigenically-distinct human coronavirus strains, 229E and OC43,<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> the SARS-causing coronavirus is a novel strain.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref></p><p id="para30">The lack of known antiviral treatment against coronaviridiae in the face of an epidemic creates a sense of urgency. The availability of agents that could modulate key events of the coronavirus replicative cycle, such as viral attachment to target cells, could have important therapeutic implications. Some insights with respect to host receptors of human coronaviridiae could help us to find ways of halting viral spread. Specifically, the human cell membrane-bound metalloproteinase, aminopeptidase N (CD13), is the receptor for coronavirus 229E (but not for OC43);<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> aminopeptidase N is also a receptor for enteropathogenic coronaviruses,<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> indicating some degree of ligand-receptor promiscuity. This cell-surface glycoprotein is expressed in many human tissues, including lungs.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Moreover, aminopeptidase N is highly expressed in immune cells and in the activated vascular endothelium of sites of inflammation,<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> potentially providing an entry site. Potent and selective inhibitors of this receptor—eg, ubenimex—do exist.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Ubenimex has been used as an oral agent with limited toxicity in patients with cancer.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Also, this drug has immunomodulatory effects<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> that might attenuate virus-induced lung injury.</p><p id="para40">Since coronaviruses are the pathogen, or important copathogens, in SARS, blockage of aminopeptidase N with ubenimex or monoclonal antibodies should be explored as a prophylaxis in high-risk groups, such as health-care workers or other individuals in close contact with infected patients. Additionally, consideration should be given for pre-emptive ubenimex therapy to travellers returning from southeast Asia who develop pneumonia.</p></body><back><ref-list id="bibl10"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ksiazek</surname><given-names>TG</given-names></name><name><surname>Erdman</surname><given-names>D</given-names></name><name><surname>Goldsmith</surname><given-names>C</given-names></name></person-group><article-title>A novel coronavirus associated with severe acute respiratory syndrome</article-title><source>N Engl J Med</source><year>April 10, 2003</year><comment>Published online</comment></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>McIntosh</surname><given-names>K</given-names></name></person-group><chapter-title>Coronaviruses</chapter-title><person-group person-group-type="editor"><name><surname>Mandell</surname><given-names>GL</given-names></name><name><surname>Bennett</surname><given-names>JE</given-names></name><name><surname>Dolin</surname><given-names>R</given-names></name></person-group><source>Mandell, Douglas and Bennett's Principle and Practice of Infectious Diseases</source><edition>5th edn.</edition><year>2000</year><publisher-name>Churchill Livingston</publisher-name><publisher-loc>Philadelphia</publisher-loc></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yeager</surname><given-names>CL</given-names></name><name><surname>Ashmun</surname><given-names>RA</given-names></name><name><surname>Williams</surname><given-names>RK</given-names></name></person-group><article-title>Human aminopeptidase N is a receptor for human coronavirus 229E</article-title><source>Nature</source><volume>357</volume><year>1992</year><fpage>420</fpage><lpage>422</lpage><pub-id pub-id-type="pmid">1350662</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delmas</surname><given-names>B</given-names></name><name><surname>Gelfi</surname><given-names>J</given-names></name><name><surname>L'Haridon</surname><given-names>R</given-names></name></person-group><article-title>Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV</article-title><source>Nature</source><volume>357</volume><year>1992</year><fpage>417</fpage><lpage>420</lpage><pub-id pub-id-type="pmid">1350661</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pasqualini</surname><given-names>R</given-names></name><name><surname>Koivunen</surname><given-names>E</given-names></name><name><surname>Kain</surname><given-names>R</given-names></name></person-group><article-title>CD13 is an angiogenesis regulator and functions a receptor for peptides that target tumor vasculature</article-title><source>Cancer Res</source><volume>60</volume><year>2000</year><fpage>722</fpage><lpage>727</lpage><pub-id pub-id-type="pmid">10676659</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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