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

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

机构地区：[1]State Key Laboratory of Agricultural Microbiology,Huazhong Agricultural University,Wuhan,430070,China [2]Key Laboratory of Preventive Veterinary Medicine in Hubei Province,College of Veterinary Medicine,Huazhong Agricultural University,Wuhan,430070,China [3]The Cooperative Innovation Center for Sustainable Pig Production,Huazhong Agricultural University,Wuhan,430070,China [4]Department of Pathology,Faculty of Veterinary Science,University of Agriculture,Faisalabad,38040,Pakistan [5]Department of Nephrology,Henan Provincial Key Laboratory of Kidney Diseases and Immunology,Henan Provincial People's Hospital,Zhengzhou,450003,China [6]Key Laboratory for Animal Health of Jiangxi Province,Nanchang,330045,China [7]Department of Preventive Veterinary Medicine,College of Animal Science and Technology,Jiangxi Agricultural University,Nanchang,330045,China [8]College of Fisheries,Huazhong Agricultural University,Wuhan,430070,China [9]National Biopesticide Engineering Research Center,Hubei Biopesticide Engineering Research Center,Hubei Academy of Agricultural Sciences,Wuhan,430070,China

出　　处：《Virologica Sinica》2022年第1期94-106,共13页中国病毒学（英文版）

基　　金：supported by National Key Research and Development Program of China(2016YFD0501102,2016YFD0500407);National Natural Science Foundation of China(31825025,32022082,32030107,32002268);Fundamental Research Funds for the Central Universities(2662018QD025);Natural Science Foundation of Hubei Province(2019CFA010)

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(IC_(50)=2.13 and 1.98μmol/L,respectively)and Zika virus(ZIKV)(IC_(50)=3.73 and 3.42μmol/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 immunofluorescence 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.

关 键 词：FLAVIVIRUSES Japanese encephalitis virus(JEV) Zika virus(ZIKV) Dehydroepiandrosterone(DHEA) ANTIVIRALS 

分 类 号：R965.1[医药卫生—药理学]