3-羟基嘧啶-2,4-二酮作为靶向病毒核糖核酸酶H的新型乙型肝炎病毒抗病毒药物。
3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H.
作者信息
Huber Andrew D, Michailidis Eleftherios, Tang Jing, Puray-Chavez Maritza N, Boftsi Maria, Wolf Jennifer J, Boschert Kelsey N, Sheridan Megan A, Leslie Maxwell D, Kirby Karen A, Singh Kamalendra, Mitsuya Hiroaki, Parniak Michael A, Wang Zhengqiang, Sarafianos Stefan G
机构信息
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
出版信息
Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.00245-17. Print 2017 Jun.
Abstract
Hepatitis B virus (HBV) RNase H (RNH) is an appealing therapeutic target due to its essential role in viral replication. RNH inhibitors (RNHIs) could help to more effectively control HBV infections. Here, we report 3-hydroxypyrimidine-2,4-diones as novel HBV RNHIs with antiviral activity. We synthesized and tested 52 analogs and found 4 that inhibit HBV RNH activity in infected cells. Importantly, 2 of these compounds inhibited HBV replication in the low micromolar range.
摘要
乙型肝炎病毒（HBV）核糖核酸酶H（RNH）因其在病毒复制中的关键作用而成为一个有吸引力的治疗靶点。RNH抑制剂（RNHIs）有助于更有效地控制HBV感染。在此，我们报告3-羟基嘧啶-2,4-二酮作为具有抗病毒活性的新型HBV RNHIs。我们合成并测试了52种类似物，发现其中4种可抑制受感染细胞中的HBV RNH活性。重要的是，这些化合物中有2种在低微摩尔浓度范围内可抑制HBV复制。
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