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

Virologica Sinica 2023年第3期38卷 459-469页

作者： Yuhang Zhang Zhenjiang Zhang Fan Zhang Jiwen Zhang Jun Jiao Min Hou Nianchao Qian Dongming Zhao Xiaofeng Zheng Xu Tan College of Veterinary Medicine Hunan Agricultural UniversityChangsha 410128China State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China Beijing Advanced Innovation Center for Structural Biology Beijing Frontier Research Center for Biological StructureMOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologySchool of Pharmaceutical SciencesTsinghua-Peking Center for Life SciencesTsinghua UniversityBeijing 100084China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601 China

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(IC_(50)=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.

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

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