揭示乙肝病毒聚合酶在新抗病毒策略中的作用。
Unveiling the roles of HBV polymerase for new antiviral strategies.
作者信息
Clark Daniel N, Hu Jianming
机构信息
The Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, PA 17033, USA.
出版信息
Future Virol. 2015;10(3):283-295. doi: 10.2217/fvl.14.113.
Abstract
Infection with HBV is common worldwide, with over 350 million chronic carriers. Chronic HBV infection is associated with cirrhosis and hepatocellular carcinoma. All currently available oral antivirals are directed against the HBV polymerase enzyme, a reverse transcriptase. HBV polymerase contains several important domains and motifs which define its functions and reveal ways to further target it. This enzyme executes many functions required for the HBV replication cycle, including viral RNA binding, RNA packaging, protein priming, template switching, DNA synthesis and RNA degradation. In addition, HBV polymerase must interact with host proteins for its functions. Future therapeutics may inhibit not only the DNA synthesis steps which are carried out by the reverse transcriptase domain (as all current antivirals do) but other domains, functions and interactions which are essential to the HBV replication cycle.
摘要
乙肝病毒（HBV）感染在全球范围内很常见，慢性携带者超过3.5亿人。慢性HBV感染与肝硬化和肝细胞癌相关。目前所有可用的口服抗病毒药物均针对HBV聚合酶，一种逆转录酶。HBV聚合酶包含几个重要的结构域和基序，这些结构域和基序决定了它的功能，并揭示了进一步靶向它的方法。这种酶执行HBV复制周期所需的许多功能，包括病毒RNA结合、RNA包装、蛋白质引发、模板转换、DNA合成和RNA降解。此外，HBV聚合酶必须与宿主蛋白相互作用以发挥其功能。未来的治疗方法可能不仅抑制由逆转录酶结构域执行的DNA合成步骤（如同所有目前的抗病毒药物那样），还抑制对HBV复制周期至关重要的其他结构域、功能和相互作用。
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