于翀,王文婧,谢知航,周正轩,王婷,范青松,王梦涵,吕岩,许家翠,艾永兴

• 1:吉林大学动物科学学院人兽共患病研究教育部重点实验室

摘要(Abstract)：

为了探寻对马立克氏病病毒(MDV)增殖具有靶向抑制作用的药物,本研究以MDV编码的去泛素化酶UL36为靶点,利用去泛素化反应体系,对2 448个化合物进行筛选,应用泛素荧光底物分析抑制物对UL36的抑制动力学,并应用MDV致鸡胚成纤维细胞(CEF)病变模型(CPE)和MDV致鸡马立克氏病(MD)模型分析抑制物对MDV在鸡细胞中复制的影响。结果发现,化合物b-AP15在高于5μmol/L浓度时可显著地非竞争性抑制3 nmol/L UL36的酶活性(P<0.01)。b-AP15对CEF的安全浓度小于1μmol/L,0.25,0.50μmol/L的b-AP15可以显著抑制MDV在CEF上的CPE形成以及在CEF细胞内的复制(P<0.01)。以2,5 mg/(kg·d) b-AP15对MDV攻毒雏鸡通过腹腔给药治疗,可显著抑制MDV在鸡T细胞内的复制(P<0.01)。这些结果说明,去泛素化酶抑制剂b-AP15可抑制MDV在鸡细胞内的复制。

关键词(KeyWords)： 去泛素化酶UL36;马立克氏病病毒;抑制剂b-AP15

Abstract:

Keywords:

基金项目(Foundation): 吉林省自然科学基金资助项目(20180101244JC);; 国家自然科学基金资助项目(31272528);; 吉林大学国家级大学生创新创业训练计划资助项目(202110183333)

作者(Author): 于翀,王文婧,谢知航,周正轩,王婷,范青松,王梦涵,吕岩,许家翠,艾永兴

DOI: 10.16303/j.cnki.1005-4545.2021.10.02

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