3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H
3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H
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DOI：
10.1128/aac.00245-17
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发表时间：
2017-06-01
影响因子：
4.9
通讯作者：
Sarafianos, Stefan G.
中科院分区：
文献类型：
--
作者：
Huber, Andrew D.;Michailidis, Eleftherios;Sarafianos, Stefan G.
B型肝炎病毒（HBV）核糖核酸酶H（RNH）由于其在病毒复制中的重要作用而成为有吸引力的治疗靶点。RNH抑制剂（RNHIs）可以帮助更有效地控制HBV感染。在这里，我们报告3-羟基嘧啶-2，4-二酮作为新的HBV RNHI与抗病毒活性。我们合成并测试了52种类似物，发现4种在感染细胞中抑制HBV RNH活性。重要的是，这些化合物中的2种在低微摩尔范围内抑制HBV复制。
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.