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Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment
Zu M(祖勉); Zu, M; Li, C; Fang, JS; Lian, WW; Liu, AL; Zheng, LS; Du, GH
2015
发表期刊MOLECULES
卷号20期号:11页码:19735-19747
文章类型Article
摘要The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery.
关键词influenza A virus CLK1 inhibitor CPE assay baculovirus coinfection protein expression and purification rational screening
学科领域Chemistry
DOI10.3390/molecules201119653
收录类别SCI ; MEDLINE
WOS类目Chemistry, Organic
WOS记录号WOS:000365924800007
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被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/228860
专题多学科研究中心
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GB/T 7714
Zu M,Zu, M,Li, C,et al. Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment[J]. MOLECULES,2015,20(11):19735-19747.
APA 祖勉.,Zu, M.,Li, C.,Fang, JS.,Lian, WW.,...&Du, GH.(2015).Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment.MOLECULES,20(11),19735-19747.
MLA 祖勉,et al."Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment".MOLECULES 20.11(2015):19735-19747.
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