Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
Identifieur interne : 000044 ( Psycho/Analysis ); précédent : 000043; suivant : 000045Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection
Auteurs : Julie Dyall [États-Unis] ; Christopher M. Coleman [États-Unis] ; Brit J. Hart [États-Unis] ; Thiagarajan Venkataraman [États-Unis] ; Michael R. Holbrook [États-Unis] ; Jason Kindrachuk [États-Unis] ; Reed F. Johnson [États-Unis] ; Gene G. Jr Olinger [États-Unis] ; Peter B. Jahrling [États-Unis] ; Monique Laidlaw [États-Unis] ; Lisa M. Johansen [États-Unis] ; Calli M. Lear-Rooney [États-Unis] ; Pamela J. Glass [États-Unis] ; Lisa E. Hensley [États-Unis] ; Matthew B. Frieman [États-Unis]Source :
- Antimicrobial agents and chemotherapy [ 0066-4804 ] ; 2014.
Descripteurs français
- KwdFr :
- Agrément de médicaments, Animaux, Antagonistes des oestrogènes (pharmacologie), Antiviraux (pharmacologie), Bibliothèques de petites molécules (pharmacologie), Cellules Vero, Concentration inhibitrice 50, Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Humains, Neuroleptiques (pharmacologie), Repositionnement des médicaments, Réplication virale (), Tests de criblage à haut débit, Virus du SRAS (), Virus du SRAS (physiologie).
- MESH :
- pharmacologie : Antagonistes des oestrogènes, Antiviraux, Bibliothèques de petites molécules, Neuroleptiques.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Virus du SRAS.
- Pascal (Inist)
- Agrément de médicaments, Animaux, Autorisation mise sur marché, Cellules Vero, Concentration inhibitrice 50, Coronavirus du syndrome respiratoire du Moyen-Orient, Humains, Indication, Chimiothérapie, Coronavirus, Infection, Repositionnement, Repositionnement des médicaments, Réplication virale, Syndrome respiratoire du Moyen-Orient, Tests de criblage à haut débit, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antipsychotic Agents (pharmacology), Antiviral Agents (pharmacology), Chemotherapy, Chlorocebus aethiops, Coronavirus, Drug Approval, Drug Repositioning, Estrogen Antagonists (pharmacology), High-Throughput Screening Assays, Humans, Indication, Infection, Inhibitory Concentration 50, Marketing authorization, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (physiology), Middle East respiratory syndrome, SARS Virus (drug effects), SARS Virus (physiology), Small Molecule Libraries (pharmacology), Vero Cells, Virus Replication (drug effects).
- MESH :
- chemical , pharmacology : Antipsychotic Agents, Antiviral Agents, Estrogen Antagonists, Small Molecule Libraries.
- drug effects : Middle East Respiratory Syndrome Coronavirus, SARS Virus, Virus Replication.
- physiology : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- Animals, Chlorocebus aethiops, Drug Approval, Drug Repositioning, High-Throughput Screening Assays, Humans, Inhibitory Concentration 50, Vero Cells.
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 in vivo studies as well as incorporation into ongoing clinical studies.
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Pascal:14-0220025Le document en format XML
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Coleman</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of Maryland School of Medicine</s1><s2>Baltimore, Maryland</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Hart, Brit J" sort="Hart, Brit J" uniqKey="Hart B" first="Brit J." last="Hart">Brit J. Hart</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Venkataraman, Thiagarajan" sort="Venkataraman, Thiagarajan" uniqKey="Venkataraman T" first="Thiagarajan" last="Venkataraman">Thiagarajan Venkataraman</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of Maryland School of Medicine</s1><s2>Baltimore, Maryland</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kindrachuk, Jason" sort="Kindrachuk, Jason" uniqKey="Kindrachuk J" first="Jason" last="Kindrachuk">Jason Kindrachuk</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><inist:fA14 i1="03"><s1>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Olinger, Gene G Jr" sort="Olinger, Gene G Jr" uniqKey="Olinger G" first="Gene G. Jr" last="Olinger">Gene G. Jr Olinger</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Laidlaw, Monique" sort="Laidlaw, Monique" uniqKey="Laidlaw M" first="Monique" last="Laidlaw">Monique Laidlaw</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Zalicus Inc.</s1><s2>Cambridge, Massachusetts</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Johansen, Lisa M" sort="Johansen, Lisa M" uniqKey="Johansen L" first="Lisa M." last="Johansen">Lisa M. Johansen</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Zalicus Inc.</s1><s2>Cambridge, Massachusetts</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></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 wicri:level="2"><inist:fA14 i1="05"><s1>United States Army Medical Research Institute of Infectious Diseases</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><inist:fA14 i1="05"><s1>United States Army Medical Research Institute of Infectious Diseases</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></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 wicri:level="2"><inist:fA14 i1="01"><s1>Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Frederick, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology and Immunology, University of Maryland School of Medicine</s1><s2>Baltimore, Maryland</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Antimicrobial agents and chemotherapy</title><title level="j" type="abbreviated">Antimicrob. agents chemother.</title><idno type="ISSN">0066-4804</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Antimicrobial agents and chemotherapy</title><title level="j" type="abbreviated">Antimicrob. agents chemother.</title><idno type="ISSN">0066-4804</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antipsychotic Agents (pharmacology)</term><term>Antiviral Agents (pharmacology)</term><term>Chemotherapy</term><term>Chlorocebus aethiops</term><term>Coronavirus</term><term>Drug Approval</term><term>Drug Repositioning</term><term>Estrogen Antagonists (pharmacology)</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Indication</term><term>Infection</term><term>Inhibitory Concentration 50</term><term>Marketing authorization</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Middle East respiratory syndrome</term><term>SARS Virus (drug effects)</term><term>SARS Virus (physiology)</term><term>Small Molecule Libraries (pharmacology)</term><term>Vero Cells</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agrément de médicaments</term><term>Animaux</term><term>Antagonistes des oestrogènes (pharmacologie)</term><term>Antiviraux (pharmacologie)</term><term>Bibliothèques de petites molécules (pharmacologie)</term><term>Cellules Vero</term><term>Concentration inhibitrice 50</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Humains</term><term>Neuroleptiques (pharmacologie)</term><term>Repositionnement des médicaments</term><term>Réplication virale ()</term><term>Tests de criblage à haut débit</term><term>Virus du SRAS ()</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antipsychotic Agents</term><term>Antiviral Agents</term><term>Estrogen Antagonists</term><term>Small Molecule Libraries</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antagonistes des oestrogènes</term><term>Antiviraux</term><term>Bibliothèques de petites molécules</term><term>Neuroleptiques</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Drug Approval</term><term>Drug Repositioning</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Vero Cells</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Agrément de médicaments</term><term>Animaux</term><term>Autorisation mise sur marché</term><term>Cellules Vero</term><term>Concentration inhibitrice 50</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Humains</term><term>Indication</term><term>Chimiothérapie</term><term>Coronavirus</term><term>Infection</term><term>Repositionnement</term><term>Repositionnement des médicaments</term><term>Réplication virale</term><term>Syndrome respiratoire du Moyen-Orient</term><term>Tests de criblage à haut débit</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 in vivo studies as well as incorporation into ongoing clinical studies.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Dyall, Julie" sort="Dyall, Julie" uniqKey="Dyall J" first="Julie" last="Dyall">Julie Dyall</name></region><name sortKey="Coleman, Christopher M" sort="Coleman, Christopher M" uniqKey="Coleman C" first="Christopher M." last="Coleman">Christopher M. Coleman</name><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B." last="Frieman">Matthew B. Frieman</name><name sortKey="Glass, Pamela J" sort="Glass, Pamela J" uniqKey="Glass P" first="Pamela J." last="Glass">Pamela J. Glass</name><name sortKey="Hart, Brit J" sort="Hart, Brit J" uniqKey="Hart B" first="Brit J." last="Hart">Brit J. Hart</name><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name><name sortKey="Holbrook, Michael R" sort="Holbrook, Michael R" uniqKey="Holbrook M" first="Michael R." last="Holbrook">Michael R. Holbrook</name><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name><name sortKey="Johansen, Lisa M" sort="Johansen, Lisa M" uniqKey="Johansen L" first="Lisa M." last="Johansen">Lisa M. Johansen</name><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name><name sortKey="Kindrachuk, Jason" sort="Kindrachuk, Jason" uniqKey="Kindrachuk J" first="Jason" last="Kindrachuk">Jason Kindrachuk</name><name sortKey="Laidlaw, Monique" sort="Laidlaw, Monique" uniqKey="Laidlaw M" first="Monique" last="Laidlaw">Monique Laidlaw</name><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><name sortKey="Olinger, Gene G Jr" sort="Olinger, Gene G Jr" uniqKey="Olinger G" first="Gene G. Jr" last="Olinger">Gene G. Jr Olinger</name><name sortKey="Venkataraman, Thiagarajan" sort="Venkataraman, Thiagarajan" uniqKey="Venkataraman T" first="Thiagarajan" last="Venkataraman">Thiagarajan Venkataraman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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