Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques
Identifieur interne : 000412 ( Pmc/Curation ); précédent : 000411; suivant : 000413Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques
Auteurs : Darryl Falzarano ; Emmie De Wit ; Angela L. Rasmussen ; Friederike Feldmann ; Atsushi Okumura ; Dana P. Scott ; Doug Brining ; Trenton Bushmaker ; Cynthia Martellaro ; Laura Baseler ; Arndt G. Benecke [France] ; Michael G. Katze ; Vincent J. Munster ; Heinz FeldmannSource :
- Nature Medicine [ 1078-8956 ] ; 2013.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) has killed ∼50% of individuals known to be infected, making understanding its mechanisms of transmission and pathogenesis and identifying candidate treatments a high priority. Heinz Feldmann, Vincent J. Munster and Michael G. Katze and their colleagues now report that treating MERS-CoV-infected rhesus macaques with interferon-α2b and ribavirin reduced virus replication and infection severity, suggesting the potential use of this combination for the clinical treatment of infected humans.
The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/nm.3362
PubMed: 24013700
PubMed Central: 4093902
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Darryl Falzarano<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, 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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques</title><author><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Rasmussen, Angela L" sort="Rasmussen, Angela L" uniqKey="Rasmussen A" first="Angela L" last="Rasmussen">Angela L. 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Rasmussen</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation></author><author><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Brining, Doug" sort="Brining, Doug" uniqKey="Brining D" first="Doug" last="Brining">Doug Brining</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Bushmaker, Trenton" sort="Bushmaker, Trenton" uniqKey="Bushmaker T" first="Trenton" last="Bushmaker">Trenton Bushmaker</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Virus Ecology Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Martellaro, Cynthia" sort="Martellaro, Cynthia" uniqKey="Martellaro C" first="Cynthia" last="Martellaro">Cynthia Martellaro</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Baseler, Laura" sort="Baseler, Laura" uniqKey="Baseler L" first="Laura" last="Baseler">Laura Baseler</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.169077.e</institution-id><institution-id institution-id-type="ISNI">0000 0004 1937 2197</institution-id><institution>Department of Comparative Pathobiology,</institution><institution>Purdue University,</institution></institution-wrap>West Lafayette, Indiana USA</nlm:aff><wicri:noCountry code="subfield">Indiana USA</wicri:noCountry></affiliation></author><author><name sortKey="Benecke, Arndt G" sort="Benecke, Arndt G" uniqKey="Benecke A" first="Arndt G" last="Benecke">Arndt G. Benecke</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff6">Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Paris, UMR7224 France</nlm:aff><orgName type="university">Université Pierre-et-Marie-Curie</orgName><country>France</country><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G" last="Katze">Michael G. Katze</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Washington National Primate Research Center, University of Washington,</institution></institution-wrap>Seattle, Washington USA</nlm:aff><wicri:noCountry code="subfield">Washington USA</wicri:noCountry></affiliation></author><author><name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J" last="Munster">Vincent J. Munster</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Virus Ecology Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</nlm:aff><wicri:noCountry code="subfield">Montana USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.21613.37</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 9609</institution-id><institution>Department of Medical Microbiology,</institution><institution>University of Manitoba,</institution></institution-wrap>Winnipeg, Manitoba Canada</nlm:aff><wicri:noCountry code="subfield">Manitoba Canada</wicri:noCountry></affiliation></author></analytic><series><title level="j">Nature Medicine</title><idno type="ISSN">1078-8956</idno><idno type="eISSN">1546-170X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The Middle East respiratory syndrome coronavirus (MERS-CoV) has killed ∼50% of individuals known to be infected, making understanding its mechanisms of transmission and pathogenesis and identifying candidate treatments a high priority. Heinz Feldmann, Vincent J. Munster and Michael G. Katze and their colleagues now report that treating MERS-CoV-infected rhesus macaques with interferon-α2b and ribavirin reduced virus replication and infection severity, suggesting the potential use of this combination for the clinical treatment of infected humans.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stockman, Lj" uniqKey="Stockman L">LJ Stockman</name></author><author><name sortKey="Bellamy, R" uniqKey="Bellamy R">R Bellamy</name></author><author><name sortKey="Garner, P" uniqKey="Garner P">P Garner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soo, Yo" uniqKey="Soo Y">YO Soo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ho, Jc" uniqKey="Ho J">JC Ho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, Y" uniqKey="Cheng Y">Y Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Booth, Cm" uniqKey="Booth C">CM Booth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Ks" uniqKey="Chan K">KS Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loutfy, Mr" uniqKey="Loutfy M">MR Loutfy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, E" uniqKey="Thomas E">E Thomas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sarasin Filipowicz, M" uniqKey="Sarasin Filipowicz M">M Sarasin-Filipowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menshykau, D" uniqKey="Menshykau D">D Menshykau</name></author><author><name sortKey="Kraemer, C" uniqKey="Kraemer C">C Kraemer</name></author><author><name sortKey="Iber, D" uniqKey="Iber D">D Iber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Teng, H" uniqKey="Teng H">H Teng</name></author><author><name sortKey="Shi, J" uniqKey="Shi J">J Shi</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, M" uniqKey="Li M">M Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, Ac" uniqKey="White A">AC White</name></author><author><name sortKey="Lavine, Kj" uniqKey="Lavine K">KJ Lavine</name></author><author><name sortKey="Ornitz, Dm" uniqKey="Ornitz D">DM Ornitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, Ac" uniqKey="White A">AC White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cigna, N" uniqKey="Cigna N">N Cigna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fitch, Pm" uniqKey="Fitch P">PM Fitch</name></author><author><name sortKey="Howie, Se" uniqKey="Howie S">SE Howie</name></author><author><name sortKey="Wallace, Wa" uniqKey="Wallace W">WA Wallace</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, G" uniqKey="Wang G">G Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pogach, Ms" uniqKey="Pogach M">MS Pogach</name></author><author><name sortKey="Cao, Y" uniqKey="Cao Y">Y Cao</name></author><author><name sortKey="Millien, G" uniqKey="Millien G">G Millien</name></author><author><name sortKey="Ramirez, Mi" uniqKey="Ramirez M">MI Ramirez</name></author><author><name sortKey="Williams, Mc" uniqKey="Williams M">MC 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Med</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Med</journal-id><journal-title-group><journal-title>Nature Medicine</journal-title></journal-title-group><issn pub-type="ppub">1078-8956</issn><issn pub-type="epub">1546-170X</issn><publisher><publisher-name>Nature Publishing Group US</publisher-name><publisher-loc>New York</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24013700</article-id><article-id pub-id-type="pmc">4093902</article-id><article-id pub-id-type="publisher-id">BFnm3362</article-id><article-id pub-id-type="doi">10.1038/nm.3362</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Falzarano</surname><given-names>Darryl</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>de Wit</surname><given-names>Emmie</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rasmussen</surname><given-names>Angela L</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Feldmann</surname><given-names>Friederike</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Okumura</surname><given-names>Atsushi</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>Dana P</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Brining</surname><given-names>Doug</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bushmaker</surname><given-names>Trenton</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Martellaro</surname><given-names>Cynthia</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Baseler</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Benecke</surname><given-names>Arndt G</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Katze</surname><given-names>Michael G</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Munster</surname><given-names>Vincent J</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Feldmann</surname><given-names>Heinz</given-names></name><address><email>feldmannh@niaid.nih.gov</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff8">8</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Disease Modeling and Transmission Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Department of Microbiology,</institution><institution>University of Washington,</institution></institution-wrap>Seattle, Washington USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000 0001 2164 9667</institution-id><institution>Division of Intramural Research,</institution><institution>Virus Ecology Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories,</institution></institution-wrap>Hamilton, Montana USA</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="GRID">grid.169077.e</institution-id><institution-id institution-id-type="ISNI">0000 0004 1937 2197</institution-id><institution>Department of Comparative Pathobiology,</institution><institution>Purdue University,</institution></institution-wrap>West Lafayette, Indiana USA</aff><aff id="Aff6"><label>6</label>Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Paris, UMR7224 France</aff><aff id="Aff7"><label>7</label><institution-wrap><institution-id institution-id-type="GRID">grid.34477.33</institution-id><institution-id institution-id-type="ISNI">0000000122986657</institution-id><institution>Washington National Primate Research Center, University of Washington,</institution></institution-wrap>Seattle, Washington USA</aff><aff id="Aff8"><label>8</label><institution-wrap><institution-id institution-id-type="GRID">grid.21613.37</institution-id><institution-id institution-id-type="ISNI">0000 0004 1936 9609</institution-id><institution>Department of Medical Microbiology,</institution><institution>University of Manitoba,</institution></institution-wrap>Winnipeg, Manitoba Canada</aff></contrib-group><pub-date pub-type="epub"><day>8</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="ppub"><year>2013</year></pub-date><volume>19</volume><issue>10</issue><fpage>1313</fpage><lpage>1317</lpage><history><date date-type="received"><day>24</day><month>5</month><year>2013</year></date><date date-type="accepted"><day>27</day><month>8</month><year>2013</year></date></history><permissions><copyright-statement>© Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2013</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1" abstract-type="web-summary"><p id="Par1">The Middle East respiratory syndrome coronavirus (MERS-CoV) has killed ∼50% of individuals known to be infected, making understanding its mechanisms of transmission and pathogenesis and identifying candidate treatments a high priority. Heinz Feldmann, Vincent J. Munster and Michael G. Katze and their colleagues now report that treating MERS-CoV-infected rhesus macaques with interferon-α2b and ribavirin reduced virus replication and infection severity, suggesting the potential use of this combination for the clinical treatment of infected humans.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users.</p></sec></abstract><abstract id="Abs2"><p id="Par2">The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths<sup><xref ref-type="bibr" rid="CR1">1</xref></sup> at the time of this article's publication. Therapeutic interventions have not been evaluated <italic>in vivo</italic>; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease<sup><xref ref-type="bibr" rid="CR2">2</xref>,<xref ref-type="bibr" rid="CR3">3</xref></sup> that recapitulates mild to moderate human MERS-CoV cases<sup><xref ref-type="bibr" rid="CR4">4</xref>,<xref ref-type="bibr" rid="CR5">5</xref></sup>. The combination of interferon-<bold>α</bold>2b and ribavirin was effective in reducing MERS-CoV replication <italic>in vitro</italic><sup><xref ref-type="bibr" rid="CR6">6</xref></sup>; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-<bold>α</bold>2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-<bold>α</bold>2b and ribavirin should be considered for the management of MERS-CoV cases.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Viral infection</kwd><kwd>Drug therapy</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s), under exclusive licence to Springer Nature America, Inc. 2013</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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