Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.
Identifieur interne : 001393 ( Main/Exploration ); précédent : 001392; suivant : 001394Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.
Auteurs : Christopher M. Coleman [États-Unis] ; Jeanne M. Sisk [États-Unis] ; Rebecca M. Mingo [États-Unis] ; Elizabeth A. Nelson [États-Unis] ; Judith M. White [États-Unis] ; Matthew B. Frieman [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Humains, Inhibiteurs de protéines kinases (pharmacologie), Lignée cellulaire, Mésylate d'imatinib (pharmacologie), Protein-tyrosine kinases (antagonistes et inhibiteurs), Pénétration virale (), Virus du SRAS (), Virus du SRAS (physiologie).
- MESH :
- antagonistes et inhibiteurs : Protein-tyrosine kinases.
- pharmacologie : Antiviraux, Inhibiteurs de protéines kinases, Mésylate d'imatinib.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Virus du SRAS.
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Humains, Lignée cellulaire, Pénétration virale, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Cell Line, Humans, Imatinib Mesylate (pharmacology), Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (physiology), Protein Kinase Inhibitors (pharmacology), Protein-Tyrosine Kinases (antagonists & inhibitors), SARS Virus (drug effects), SARS Virus (physiology), Virus Internalization (drug effects).
- MESH :
- chemical , antagonists & inhibitors : Protein-Tyrosine Kinases.
- chemical , pharmacology : Antiviral Agents, Imatinib Mesylate, Protein Kinase Inhibitors.
- drug effects : Middle East Respiratory Syndrome Coronavirus, SARS Virus, Virus Internalization.
- physiology : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- Animals, Cell Line, Humans.
Abstract
The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses.
DOI: 10.1128/JVI.01429-16
PubMed: 27466418
Affiliations:
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There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Virginie</li></region><settlement><li>College Park (Maryland)</li></settlement><orgName><li>Université du Maryland</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Coleman, Christopher M" sort="Coleman, Christopher M" uniqKey="Coleman C" first="Christopher M" last="Coleman">Christopher M. Coleman</name></region><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><name sortKey="Mingo, Rebecca M" sort="Mingo, Rebecca M" uniqKey="Mingo R" first="Rebecca M" last="Mingo">Rebecca M. Mingo</name><name sortKey="Nelson, Elizabeth A" sort="Nelson, Elizabeth A" uniqKey="Nelson E" first="Elizabeth A" last="Nelson">Elizabeth A. Nelson</name><name sortKey="Sisk, Jeanne M" sort="Sisk, Jeanne M" uniqKey="Sisk J" first="Jeanne M" last="Sisk">Jeanne M. Sisk</name><name sortKey="White, Judith M" sort="White, Judith M" uniqKey="White J" first="Judith M" last="White">Judith M. White</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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