rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
7
|
pubmed:dateCreated |
2009-6-25
|
pubmed:abstractText |
Enterovirus 71 (EV71) has emerged as an important virulent neurotropic enterovirus in young children. DTriP-22 (4{4-[(2-bromo-phenyl)-(3-methyl-thiophen-2-yl)-methyl]-piperazin-1-yl}-1-pheny-1H-pyrazolo[3,4-d]pyrimidine) was found to be a novel and potent inhibitor of EV71. The molecular target of this compound was identified by analyzing DTriP-22-resistant viruses. A substitution of lysine for Arg163 in EV71 3D polymerase rendered the virus drug resistant. DTriP-22 exhibited the ability to inhibit viral replication by reducing viral RNA accumulation. The compound suppressed the accumulated levels of both positive- and negative-stranded viral RNA during virus infection. An in vitro polymerase assay indicated that DTriP-22 inhibited the poly(U) elongation activity, but not the VPg uridylylation activity, of EV71 polymerase. These findings demonstrate that the nonnucleoside analogue DTriP-22 acts as a novel inhibitor of EV71 polymerase. DTriP-22 also exhibited a broad spectrum of antiviral activity against other picornaviruses, which highlights its potential in the development of antiviral agents.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jul
|
pubmed:issn |
1098-6596
|
pubmed:author |
|
pubmed:issnType |
Electronic
|
pubmed:volume |
53
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2740-7
|
pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19414569-Animals,
pubmed-meshheading:19414569-Antiviral Agents,
pubmed-meshheading:19414569-Cell Line, Tumor,
pubmed-meshheading:19414569-Cercopithecus aethiops,
pubmed-meshheading:19414569-Dogs,
pubmed-meshheading:19414569-Enterovirus,
pubmed-meshheading:19414569-Enterovirus Infections,
pubmed-meshheading:19414569-HeLa Cells,
pubmed-meshheading:19414569-Humans,
pubmed-meshheading:19414569-RNA Replicase,
pubmed-meshheading:19414569-Recombinant Proteins,
pubmed-meshheading:19414569-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19414569-Vero Cells
|
pubmed:year |
2009
|
pubmed:articleTitle |
Novel antiviral agent DTriP-22 targets RNA-dependent RNA polymerase of enterovirus 71.
|
pubmed:affiliation |
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, 259 Wen-Hua 1st Rd., Kwei-Shan, Taoyuan, Taiwan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|