Unveiling the roles of HBV polymerase for new antiviral strategies.

Unveiling the roles of HBV polymerase for new antiviral strategies.
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DOI:
10.2217/fvl.14.113
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发表时间:
2015
期刊:
影响因子:
3.1
通讯作者:
Hu J
Hu J
中科院分区:
医学4区
文献类型:
--
作者:
Clark DN;Hu J

文献摘要

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HBV感染在世界范围内很常见,有超过3.5亿慢性携带者。慢性HBV感染与肝硬化和肝细胞癌有关。所有目前可用的口服抗病毒药物都是针对HBV聚合酶(一种逆转录酶)的。HBV聚合酶包含几个重要的结构域和基序,这些结构域和基序定义了HBV聚合酶的功能,并揭示了进一步靶向HBV聚合酶的方法。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质相互作用才能发挥其功能。未来的治疗可能不仅抑制由逆转录酶结构域进行的DNA合成步骤(如所有当前的抗病毒药物所做的那样),而且抑制对HBV复制周期至关重要的其他结构域、功能和相互作用。
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.