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Screening for novel small molecule inhibitors targeting the assembling of influenza virus polymerase complex by a BiLC-based reporter system.

J Virol.. 2016-12; 
Li C, Wang Z, Cao Y, Wang L, Ji J, Chen Z, Deng T, Jiang T, Cheng G, Qin FX. Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China.
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摘要

Influenza virus RNA-dependent RNA polymerase consists of three viral protein subunits: PA, PB1 and PB2. Protein-protein interactions (PPIs) of these subunits play pivotal roles in assembling the functional polymerase complex, which is essential for the replication and transcription of influenza virus RNA. Here we developed a highly specific and robust bimolecular luminescence complementation (BiLC) reporter system to facilitate the investigation for influenza virus polymerase complex formation. Furthermore, by combining computational modeling and the BiLC reporter assay, we identified several novel small molecule compounds that selectively inhibited PB1-PB2 interaction. Function of one such lead compound was co... More

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