Screening of novel synthetic derivatives of dehydroepiandrosterone for antivirals against flaviviruses infections

文献类型： 外文期刊

第一作者： Imran, Muhammad

作者： Imran, Muhammad;Zhang, Luping;Zheng, Bohan;Zhao, Zikai;Zhou, Dengyuan;Duan, Hongyu;Li, Qiuyan;Cao, Shengbo;Ye, Jing;Imran, Muhammad;Zhang, Luping;Zheng, Bohan;Zhao, Zikai;Zhou, Dengyuan;Duan, Hongyu;Li, Qiuyan;Cao, Shengbo;Ye, Jing;Imran, Muhammad;Zhang, Luping;Zheng, Bohan;Zhao, Zikai;Zhou, Dengyuan;Duan, Hongyu;Li, Qiuyan;Cao, Shengbo;Ye, Jing;Imran, Muhammad;Wan, Shengfeng;Chen, Zheng;Chen, Zheng;Liu, Xueqin;Ke, Shaoyong

作者机构：

关键词： Flaviviruses; Japanese encephalitis virus (JEV); Zika virus (ZIKV); Dehydroepiandrosterone (DHEA); Antivirals

期刊名称：VIROLOGICA SINICA （ 影响因子：6.947； 五年影响因子：5.997 ）

ISSN： 1674-0769

年卷期： 2022 年 37 卷 1 期

页码：

收录情况： SCI

摘要： Flaviviruses are important arthropod-borne pathogens that represent an immense global health problem. Their unprecedented epidemic rate and unpredictable clinical features underscore an urgent need for antiviral interventions. Dehydroepiandrosterone (DHEA) is a natural occurring adrenal-derived steroid in the human body that has been associated in protection against various infections. In the present study, the plaque assay based primary screening was conducted on 32 synthetic derivatives of DHEA against Japanese encephalitis virus (JEV) to identify potent anti-flaviviral compounds. Based on primary screening, HAAS-AV3026 and HAAS-AV3027 were selected as hits from DHEA derivatives that exhibited strong antiviral activity against JEV (IC50 = 2.13 and 1.98 mu mol/L, respectively) and Zika virus (ZIKV) (IC50 = 3.73 and 3.42 mu mol/L, respectively). Mechanism study indicates that HAAS-AV3026 and HAAS-AV3027 do not exhibit inhibitory effect on flavivirus binding and entry process, while significantly inhibit flavivirus infection at the replication stage. Moreover, indirect immunofluo-rescence assay, Western blot analyses, and quantitative reverse transcription-PCR (qRT-PCR) revealed a potent antiviral activity of DHEA derivatives hits against JEV and ZIKV in terms of inhibition of viral infection, protein production, and viral RNA synthesis in Vero cells. Taken together, our results may provide a basis for the development of new antivirals against flaviviruses.

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