Source:http://linkedlifedata.com/resource/pubmed/id/21507972
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2011-6-10
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pubmed:abstractText |
Coronaviruses are a family of enveloped single-stranded positive-sense RNA viruses causing respiratory, enteric, and neurologic diseases in mammals and fowl. Human coronaviruses are recognized to cause up to a third of common colds and are suspected to be involved in enteric and neurologic diseases. Coronavirus replication involves the generation of nested subgenomic mRNAs (sgmRNAs) with a common capped 5' leader sequence. The translation of most of the sgmRNAs is thought to be cap dependent and displays a requirement for eukaryotic initiation factor 4F (eIF4F), a heterotrimeric complex needed for the recruitment of 40S ribosomes. We recently reported on an ultrahigh-throughput screen to discover compounds that inhibit eIF4F activity by blocking the interaction of two of its subunits (R. Cencic et al., Proc. Natl. Acad. Sci. U. S. A. 108:1046-1051, 2011). Herein we describe a molecule from this screen that prevents the interaction between eIF4E (the cap-binding protein) and eIF4G (a large scaffolding protein), inhibiting cap-dependent translation. This inhibitor significantly decreased human coronavirus 229E (HCoV-229E) replication, reducing the percentage of infected cells and intra- and extracellular infectious virus titers. Our results support the strategy of targeting the eIF4F complex to block coronavirus infection.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-4E,
http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-4G,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Caps,
http://linkedlifedata.com/resource/pubmed/chemical/Small Molecule Libraries,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1098-5514
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pubmed:author |
pubmed-author:CencicReginaR,
pubmed-author:DesforgesMarcM,
pubmed-author:DingledineRaymondR,
pubmed-author:DuYuhongY,
pubmed-author:FuHaianH,
pubmed-author:HallDavid RDR,
pubmed-author:KozakovDimaD,
pubmed-author:MinJaekiJ,
pubmed-author:PelletierJerryJ,
pubmed-author:TalbotPierre JPJ,
pubmed-author:VajdaSandorS
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pubmed:issnType |
Electronic
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6381-9
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pubmed:meshHeading |
pubmed-meshheading:21507972-Antiviral Agents,
pubmed-meshheading:21507972-Cell Line,
pubmed-meshheading:21507972-Coronavirus 229E, Human,
pubmed-meshheading:21507972-Drug Discovery,
pubmed-meshheading:21507972-Eukaryotic Initiation Factor-4E,
pubmed-meshheading:21507972-Eukaryotic Initiation Factor-4G,
pubmed-meshheading:21507972-High-Throughput Screening Assays,
pubmed-meshheading:21507972-Humans,
pubmed-meshheading:21507972-Protein Biosynthesis,
pubmed-meshheading:21507972-RNA Caps,
pubmed-meshheading:21507972-Small Molecule Libraries,
pubmed-meshheading:21507972-Viral Proteins,
pubmed-meshheading:21507972-Virus Replication
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pubmed:year |
2011
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pubmed:articleTitle |
Blocking eIF4E-eIF4G interaction as a strategy to impair coronavirus replication.
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pubmed:affiliation |
McIntyre Medical Sciences Building, Rm. 810, 3655 Promenade Sir William Osler, McGill University, Montreal, Quebec, Canada H3G 1Y6.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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