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Biochem Biophys Res Commun. 2020 Jan 15. pii: S0006-291X(20)30046-2. doi: 10.1016/j.bbrc.2019.12.099. [Epub ahead of print]
Nobiletin, a novel inhibitor, inhibits HBsAg production and hepatitis B virus replication.
Hu Z1, Hu J1, Ren F1, Xu H1, Tan M1, Wang Q1, Ren J2.
Author information
1
The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
2
The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
Abstract
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.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
Anti-HBV agents; Hepatitis B surface antigen (HBsAg); Hepatitis B virus (HBV); Nobiletin(NOB)
PMID:
31954513
DOI:
10.1016/j.bbrc.2019.12.099
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