Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
Identifieur interne : 000C40 ( Pmc/Corpus ); précédent : 000C39; suivant : 000C41Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
Auteurs : Julie Dyall ; Christopher M. Coleman ; Brit J. Hart ; Thiagarajan Venkataraman ; Michael R. Holbrook ; Jason Kindrachuk ; Reed F. Johnson ; Gene G. Olinger ; Peter B. Jahrling ; Monique Laidlaw ; Lisa M. Johansen ; Calli M. Lear-Rooney ; Pamela J. Glass ; Lisa E. Hensley ; Matthew B. FriemanSource :
- Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2014.
Abstract
Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for
Url:
DOI: 10.1128/AAC.03036-14
PubMed: 24841273
PubMed Central: 4136000
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<author><name sortKey="Olinger, Gene G" sort="Olinger, Gene G" uniqKey="Olinger G" first="Gene G." last="Olinger">Gene G. Olinger</name>
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<author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name>
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</affiliation>
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</affiliation>
</author>
<author><name sortKey="Laidlaw, Monique" sort="Laidlaw, Monique" uniqKey="Laidlaw M" first="Monique" last="Laidlaw">Monique Laidlaw</name>
<affiliation><nlm:aff id="aff4">Zalicus Inc., Cambridge, Massachusetts, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Johansen, Lisa M" sort="Johansen, Lisa M" uniqKey="Johansen L" first="Lisa M." last="Johansen">Lisa M. Johansen</name>
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</affiliation>
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<author><name sortKey="Lear Rooney, Calli M" sort="Lear Rooney, Calli M" uniqKey="Lear Rooney C" first="Calli M." last="Lear-Rooney">Calli M. Lear-Rooney</name>
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</affiliation>
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<author><name sortKey="Glass, Pamela J" sort="Glass, Pamela J" uniqKey="Glass P" first="Pamela J." last="Glass">Pamela J. Glass</name>
<affiliation><nlm:aff id="aff5">United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection</title>
<author><name sortKey="Dyall, Julie" sort="Dyall, Julie" uniqKey="Dyall J" first="Julie" last="Dyall">Julie Dyall</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coleman, Christopher M" sort="Coleman, Christopher M" uniqKey="Coleman C" first="Christopher M." last="Coleman">Christopher M. Coleman</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Hart, Brit J" sort="Hart, Brit J" uniqKey="Hart B" first="Brit J." last="Hart">Brit J. Hart</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Venkataraman, Thiagarajan" sort="Venkataraman, Thiagarajan" uniqKey="Venkataraman T" first="Thiagarajan" last="Venkataraman">Thiagarajan Venkataraman</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Holbrook, Michael R" sort="Holbrook, Michael R" uniqKey="Holbrook M" first="Michael R." last="Holbrook">Michael R. Holbrook</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kindrachuk, Jason" sort="Kindrachuk, Jason" uniqKey="Kindrachuk J" first="Jason" last="Kindrachuk">Jason Kindrachuk</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name>
<affiliation><nlm:aff id="aff3">Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Olinger, Gene G" sort="Olinger, Gene G" uniqKey="Olinger G" first="Gene G." last="Olinger">Gene G. Olinger</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laidlaw, Monique" sort="Laidlaw, Monique" uniqKey="Laidlaw M" first="Monique" last="Laidlaw">Monique Laidlaw</name>
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</affiliation>
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<author><name sortKey="Johansen, Lisa M" sort="Johansen, Lisa M" uniqKey="Johansen L" first="Lisa M." last="Johansen">Lisa M. Johansen</name>
<affiliation><nlm:aff id="aff4">Zalicus Inc., Cambridge, Massachusetts, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lear Rooney, Calli M" sort="Lear Rooney, Calli M" uniqKey="Lear Rooney C" first="Calli M." last="Lear-Rooney">Calli M. Lear-Rooney</name>
<affiliation><nlm:aff id="aff5">United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Glass, Pamela J" sort="Glass, Pamela J" uniqKey="Glass P" first="Pamela J." last="Glass">Pamela J. Glass</name>
<affiliation><nlm:aff id="aff5">United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name>
<affiliation><nlm:aff id="aff1">Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff>
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<front><div type="abstract" xml:lang="en"><p>Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for <italic>in vivo</italic>
studies as well as incorporation into ongoing clinical studies.</p>
</div>
</front>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Antimicrob Agents Chemother</journal-id>
<journal-id journal-id-type="iso-abbrev">Antimicrob. Agents Chemother</journal-id>
<journal-id journal-id-type="hwp">aac</journal-id>
<journal-id journal-id-type="pmc">aac</journal-id>
<journal-id journal-id-type="publisher-id">AAC</journal-id>
<journal-title-group><journal-title>Antimicrobial Agents and Chemotherapy</journal-title>
</journal-title-group>
<issn pub-type="ppub">0066-4804</issn>
<issn pub-type="epub">1098-6596</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
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<article-meta><article-id pub-id-type="pmid">24841273</article-id>
<article-id pub-id-type="pmc">4136000</article-id>
<article-id pub-id-type="publisher-id">03036-14</article-id>
<article-id pub-id-type="doi">10.1128/AAC.03036-14</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Antiviral Agents</subject>
</subj-group>
</article-categories>
<title-group><article-title>Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Dyall</surname>
<given-names>Julie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coleman</surname>
<given-names>Christopher M.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hart</surname>
<given-names>Brit J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Venkataraman</surname>
<given-names>Thiagarajan</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Holbrook</surname>
<given-names>Michael R.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kindrachuk</surname>
<given-names>Jason</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Johnson</surname>
<given-names>Reed F.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Olinger</surname>
<given-names>Gene G.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jahrling</surname>
<given-names>Peter B.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Laidlaw</surname>
<given-names>Monique</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Johansen</surname>
<given-names>Lisa M.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lear-Rooney</surname>
<given-names>Calli M.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Glass</surname>
<given-names>Pamela J.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hensley</surname>
<given-names>Lisa E.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Frieman</surname>
<given-names>Matthew B.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</aff>
<aff id="aff2"><label>b</label>
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA</aff>
<aff id="aff3"><label>c</label>
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA</aff>
<aff id="aff4"><label>d</label>
Zalicus Inc., Cambridge, Massachusetts, USA</aff>
<aff id="aff5"><label>e</label>
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA</aff>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Matthew B. Frieman, <email>MFrieman@som.umaryland.edu</email>
.</corresp>
<fn fn-type="equal"><p>J.D. and C.M.C. contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>8</month>
<year>2014</year>
</pub-date>
<volume>58</volume>
<issue>8</issue>
<fpage>4885</fpage>
<lpage>4893</lpage>
<history><date date-type="received"><day>10</day>
<month>4</month>
<year>2014</year>
</date>
<date date-type="rev-request"><day>2</day>
<month>5</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>14</day>
<month>5</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zac00814004885.pdf"></self-uri>
<abstract><p>Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for <italic>in vivo</italic>
studies as well as incorporation into ongoing clinical studies.</p>
</abstract>
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