期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 9, 页码 3767-3793出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00499
关键词
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资金
- Czech Science Foundation [15-09310S, 15-21030Y]
- Academy of Sciences Czech Republic [61388963]
- MarieCurie FP7-PEOPLE-CIG project [333916]
- Ministry of Education of the Czech Republic [LO1302]
- Gilead Sciences, Inc.
- European Community's Seventh Framework Programme [283570]
Phosphatidylinositol 4-kinase III beta is a cellular lipid kinase pivotal to pathogenesis of various RNA viruses. These viruses hijack the enzyme in order to modify the structure of intracellular membranes and use them for the construction of functional replication machinery. Selective inhibitors of this enzyme are potential broad-spectrum antiviral agents, as inhibition of this enzyme results in the arrest of replication of PI4K III beta-dependent viruses. Herein, we report a detailed study of novel selective inhibitors of PI4K III beta, which exert antiviral activity against a panel of single-stranded positive-sense RNA viruses. Our crystallographic data show that the inhibitors occupy the binding site for the adenine ring of the ATP molecule and therefore prevent the phosphorylation reaction.
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