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

doi:10.1016/j.virs.2023.03.004

June 2023

Citation: Yuhang Zhang, Zhenjiang Zhang, Fan Zhang, Jiwen Zhang, Jun Jiao, Min Hou, Nianchao Qian, Dongming Zhao, Xiaofeng Zheng, Xu Tan. ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound .VIROLOGICA SINICA, 2023, 38(3) : 459-469. http://dx.doi.org/10.1016/j.virs.2023.03.004

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

Yuhang Zhang ^a ,
Zhenjiang Zhang ^b ,
Fan Zhang ^c ,
Jiwen Zhang ^b ,
Jun Jiao ^c ,
Min Hou ^c ,
Nianchao Qian ^c ,
Dongming Zhao ^{b
,,} ,
Xiaofeng Zheng ^{a
,,} ,
Xu Tan ^{c,d
,,}

a. College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China;
b. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150009, China;
c. 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;
d. Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601 China

Corresponding author: Dongming Zhao, zhaodongming@caas.cn
Xiaofeng Zheng, zheng.x@hunau.edu.cn
Xu Tan, mosaictan@hotmail.com
Received Date: 25 October 2022
Accepted Date: 15 March 2023
Available online: 21 March 2023

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

Electronic Supplementary Material

10.1016j.virs.2023.03.004-ESM.docx
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