中国病毒学2023,Vol.38Issue(3) :459-469.DOI:10.1016/j.virs.2023.03.004

ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound

Yuhang Zhang Zhenjiang Zhang Fan Zhang Jiwen Zhang Jun Jiao Min Hou Nianchao Qian Dongming Zhao Xiaofeng Zheng Xu Tan
中国病毒学2023,Vol.38Issue(3) :459-469.DOI:10.1016/j.virs.2023.03.004

ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound

Yuhang Zhang 1Zhenjiang Zhang 2Fan Zhang 3Jiwen Zhang 2Jun Jiao 3Min Hou 3Nianchao Qian 3Dongming Zhao 2Xiaofeng Zheng 1Xu Tan4
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作者信息

  • 1. College of Veterinary Medicine,Hunan Agricultural University,Changsha 410128,China
  • 2. State Key Laboratory of Veterinary Biotechnology,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin 150009,China
  • 3. Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology,School of Pharmaceutical Sciences,Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing 100084,China
  • 4. Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology,School of Pharmaceutical Sciences,Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing 100084,China;Institute of Health and Medicine,Hefei Comprehensive National Science Center,Hefei 230601 China
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Abstract

African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF control.African swine fever virus(ASFV)is the etiological agent of ASF.Among the ASFV proteins,p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design.Here,we con-structed a luciferase reporter system driven by the promoter of p72,which is transcribed by the co-transfected ASFV RNA polymerase complex.Using this system,we screened over 3200 natural product compounds and obtained three potent candidates against ASFV.We further evaluated the anti-ASFV effects and proved that among the three candidates,ailanthone(AIL)inhibits the replication of ASFV at the nanomolar concentration(IC50=15 nmol/L).Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone.Finally,we showed the antiviral activity of AIL on Zika virus and hepatitis B virus(HBV),which supports that AIL is a potential broad-spectrum antiviral agent.

Key words

African swine fever virus(ASFV)/Replication inhibition/Broad-spectrum antiviral drugs/Ailanthone(AIL)

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基金项目

State Key R&D Project to Xu Tan(2022YFE0102200)

Department of Science and Technology of Hunan Province to Xiaofeng Zheng(2019RS1050)

Department of Science and Technology of Hunan Province to Xiaofeng Zheng(2021JJ30354)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所,中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子:0.393
ISSN:1674-0769
参考文献量38
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