文献类型： 外文期刊

作者： Imran, Muhammad ¹ ; Zhang, Luping ¹ ; Zheng, Bohan ¹ ; Zhao, Zikai ¹ ; Zhou, Dengyuan ¹ ; Wan, Shengfeng ⁵ ; Chen, Zheng ⁶ ; Duan, Hongyu ¹ ; Li, Qiuyan ¹ ; Liu, Xueqin ⁸ ; Cao, Shengbo ¹ ; Ke, Shaoyong ⁹ ; Ye, Jing ¹ ;

作者机构： 1.Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan 430070, Peoples R China

2.Huazhong Agr Univ, Coll Vet Med, Key Lab Prevent Vet Med Hubei Prov, Wuhan 430070, Peoples R China

3.Huazhong Agr Univ, Cooperat Innovat Ctr Sustainable Pig Prod, Wuhan 430070, Peoples R China

4.Univ Agr Faisalabad, Fac Vet Sci, Dept Pathol, Faisalabad 38040, Pakistan

5.Henan Prov Peoples Hosp, Dept Nephrol, Henan Prov Key Lab Kidney Dis & Immunol, Zhengzhou 450003, Peoples R China

6.Key Lab Anim Hlth Jiangxi Prov, Nanchang 330045, Jiangxi, Peoples R China

7.Jiangxi Agr Univ, Coll Anim Sci & Technol, Dept Prevent Vet Med, Nanchang 330045, Jiangxi, Peoples R China

8.Huazhong Agr Univ, Coll Fisheries, Wuhan 430070, Peoples R China

9.Hubei Acad Agr Sci, Natl Biopesticide Engn Res Ctr, Hubei Biopesticide Engn Res Ctr, Wuhan 430070, Peoples R China

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.