Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.
Identifieur interne : 001724 ( Ncbi/Merge ); précédent : 001723; suivant : 001725Abelson 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
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pubmed:27466418Le document en format XML
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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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27466418</PMID><DateCompleted><Year>2017</Year><Month>05</Month><Day>09</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>90</Volume><Issue>19</Issue><PubDate><Year>2016</Year><Month>10</Month><Day>01</Day></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.</ArticleTitle><Pagination><MedlinePgn>8924-33</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01429-16</ELocationID><Abstract><AbstractText Label="UNLABELLED">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.</AbstractText><AbstractText Label="IMPORTANCE">Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.</AbstractText><CopyrightInformation>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Coleman</LastName><ForeName>Christopher M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sisk</LastName><ForeName>Jeanne M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mingo</LastName><ForeName>Rebecca M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nelson</LastName><ForeName>Elizabeth A</ForeName><Initials>EA</Initials><AffiliationInfo><Affiliation>Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>White</LastName><ForeName>Judith M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frieman</LastName><ForeName>Matthew B</ForeName><Initials>MB</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA mfrieman@som.umaryland.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>F32 AI118303</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI095569</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI114776</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AI103601</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>09</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>8A1O1M485B</RegistryNumber><NameOfSubstance UI="D000068877">Imatinib Mesylate</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.-</RegistryNumber><NameOfSubstance UI="C426236">ARG tyrosine kinase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D011505">Protein-Tyrosine Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" 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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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