Generation of A Stable GFP-reporter Zika Virus System for High-throughput Screening of Zika Virus Inhibitors

文献类型： 外文期刊

第一作者： Zhang, Jing-Wei

作者： Zhang, Jing-Wei;Wang, Han;Liu, Jing;Ma, Le;Hua, Rong-Hong;Bu, Zhi-Gao;Bu, Zhi-Gao

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关键词： Zika virus (ZIKV); GFP reporter virus; High-throughput screening; Antiviral drug discovery

期刊名称：VIROLOGICA SINICA （ 影响因子：4.327； 五年影响因子：4.08 ）

ISSN： 1674-0769

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收录情况： SCI

摘要： Zika virus (ZIKV) is associated with severe birth defects and Guillain-Barre syndrome and no approved vaccines or specific therapies to combat ZIKV infection are currently available. To accelerate anti-ZIKV therapeutics research, we developed a stable ZIKV GFP-reporter virus system with considerably improved GFP visibility and stability. In this system a BHK-21 cell line expressing DC-SIGNR was established to facilitate the proliferation of GFP-reporter ZIKV. Using this reporter virus system, we established a high-throughput screening assay and screened a selected plant-sourced compounds library for their ability to block ZIKV infection. More than 31 out of 974 tested compounds effectively decreased ZIKV reporter infection. Four selected compounds, homoharringtonine (HHT), bruceine D (BD), dihydroartemisinin (DHA) and digitonin (DGT), were further validated to inhibit wild-type ZIKV infection in cells of BHK-21 and human cell line A549. The FDA-approved chronic myeloid leukemia treatment drug HHT and BD were identified as broad-spectrum flavivirus inhibitors. DHA, another FDA-approved antimalarial drug effectively inhibited ZIKV infection in BHK-21 cells. HHT, BD and DHA inhibited ZIKV infection at a post-entry stage. Digitonin was found to have inhibitory activity in the early stage of viral infection. Our research provides an efficient high-throughput screening assay for ZIKV inhibitors. The active compounds identified in this study represent potential therapies for the treatment of ZIKV infection.

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