Nobiletin, a novel inhibitor, inhibits HBsAg production and hepatitis B virus replication
Nobiletin, a novel inhibitor, inhibits HBsAg production and hepatitis B virus replication
复制标题
Nobiletin 是一种新型抑制剂，可抑制 HBsAg 的产生和乙型肝炎病毒的复制。
DOI：
10.1016/j.bbrc.2019.12.099
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发表时间：
2020-03-12
影响因子：
3.1
通讯作者：
Ren, Jihua
中科院分区：
文献类型：
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作者：
Hu, Zhongwen;Hu, Jieli;Ren, Jihua
慢性乙型肝炎病毒（HBV）感染是一个严重的问题，因为它在世界范围内广泛分布，预后差，包括肝硬化和/或肝细胞癌。乙型肝炎表面抗原（HBsAg）是HBV感染的重要血清标志物，也是有效清除病毒的主要障碍。然而，目前的抗hbv药物，如核苷(t)类似物（NA）和PegIFN，不能达到持续HBsAg损失（定义为功能治愈）的理想结果。因此，迫切需要寻找一种新的靶向HBsAg的化合物。在这项研究中，从1500种化合物中筛选出了诺比列素，因为它具有低细胞毒性和高抗病毒活性。在HepG2.2.15和HepG2-NTCP细胞中检测诺百列素对HBV的抑制作用。此外，诺比列素的抗病毒能力也在体内得到了验证。与恩替卡韦（ETV）治疗不同，诺百列素在体内和体外均能显著降低HBsAg水平和HBV DNA水平，而恩替卡韦能降低HBV DNA水平，但不能有效降低HBsAg。同时，诺百列素和ETV联合使用可广泛降低HBV DNA和HBsAg水平。这项研究可能有助于开发一类新的抗hbv药物。(C) 2020爱思唯尔公司版权所有。
Chronic hepatitis B virus (HBV) infection is a serious problem due to its extensive worldwide distribution and poor prognosis including cirrhosis and/or hepatocellular carcinoma. The hepatitis B surface antigen(HBsAg) is a vital serum marker in HBV infection and a major obstacle for effective and subsequently virus clearance. However, Current anti-HBV drugs, such as nucleos(t)ide analogs (NA) and PegIFN, do not meet ideal result of sustained HBsAg loss (defined as functional cure). Therefore, there is an urgent need to identify a new compound targeting HBsAg. In this study, nobiletin was screened out from 1500 compounds due to its low cytotoxicity and high antiviral activity. The effect of nobiletin on HBV was determined in HepG2.2.15 and HepG2-NTCP cells. Furthermore, the antiviral capability of nobiletin was also verified in vivo. Unlike entecavir (ETV) therapy, which reduced HBV DNA but do not lead to an effective reduction in HBsAg, nobiletin significantly reduced the level of HBsAg as well as lowered HBV DNA in vivo and in vitro. Meanwhile, combination of nobiletin and ETV led to broad reductions of both HBV DNA and HBsAg level. This study may shed light on the development of a novel class of anti-HBV agents. (C) 2020 Elsevier Inc. All rights reserved.