鉴定靶向痘苗病毒持续因子的蛋白-蛋白相互作用抑制剂，用于开发抗病毒药物。
Identification of protein-protein interaction inhibitors targeting vaccinia virus processivity factor for development of antiviral agents.
机构信息
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
出版信息
Antimicrob Agents Chemother. 2011 Nov;55(11):5054-62. doi: 10.1128/AAC.00278-11. Epub 2011 Aug 15.
Abstract
Poxvirus uracil DNA glycosylase D4 in association with A20 and the catalytic subunit of DNA polymerase forms the processive polymerase complex. The binding of D4 and A20 is essential for processive polymerase activity. Using an AlphaScreen assay, we identified compounds that inhibit protein-protein interactions between D4 and A20. Effective interaction inhibitors exhibited both antiviral activity and binding to D4. These results suggest that novel antiviral agents that target the protein-protein interactions between D4 and A20 can be developed for the treatment of infections with poxviruses, including smallpox.
摘要
痘病毒尿嘧啶 DNA 糖基化酶 D4 与 A20 和 DNA 聚合酶的催化亚基形成连续聚合酶复合物。D4 和 A20 的结合对于连续聚合酶活性是必需的。使用 AlphaScreen 测定法，我们鉴定出抑制 D4 和 A20 之间蛋白-蛋白相互作用的化合物。有效的相互作用抑制剂既表现出抗病毒活性又与 D4 结合。这些结果表明，可以针对痘病毒（包括天花病毒）之间的 D4 和 A20 蛋白-蛋白相互作用开发新型抗病毒药物来治疗感染。
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