Source:http://linkedlifedata.com/resource/pubmed/id/10228078
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1999-6-21
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pubmed:abstractText |
Pleconaril (VP 63843) is a novel orally bioavailable small molecule with broad antipicornavirus (enterovirus and rhinovirus) activity. Ten independently derived pleconaril-resistant variants of coxsackievirus B3 were isolated from cell culture. The molecular basis of drug resistance and the biologic properties of the drug-resistant viruses were investigated. RNA sequence analysis revealed amino acid changes in the drug-binding pocket of the resistant variants. Thermal stability studies showed the drug-resistant viruses to be significantly less stable than wild type virus. When evaluated in a murine model in which wild type virus infection is 100% lethal, the drug-resistant viruses showed attenuated virulence with both reduced mortality and delayed time to death. Virus titers in heart and spleen were dramatically lower in drug-resistant virus-infected mice than in wild type virus-infected animals. The study results indicate that pleconaril-resistant virus variants are attenuated and significantly less virulent than drug-sensitive wild type virus.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Capsid Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/pleconaril
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1899
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
179
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1538-41
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10228078-Animals,
pubmed-meshheading:10228078-Antiviral Agents,
pubmed-meshheading:10228078-Binding Sites,
pubmed-meshheading:10228078-Capsid,
pubmed-meshheading:10228078-Capsid Proteins,
pubmed-meshheading:10228078-Drug Resistance, Microbial,
pubmed-meshheading:10228078-Enterovirus B, Human,
pubmed-meshheading:10228078-Genetic Variation,
pubmed-meshheading:10228078-Male,
pubmed-meshheading:10228078-Mice,
pubmed-meshheading:10228078-Mice, Inbred BALB C,
pubmed-meshheading:10228078-Oxadiazoles,
pubmed-meshheading:10228078-RNA, Viral,
pubmed-meshheading:10228078-Sequence Analysis, RNA
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pubmed:year |
1999
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pubmed:articleTitle |
Attenuated virulence of pleconaril-resistant coxsackievirus B3 variants.
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pubmed:affiliation |
ViroPharma Incorporated, Exton, PA 19341, USA. jgroarke@viropharma.com
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pubmed:publicationType |
Journal Article
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