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Published on: May 10, 2022
Nobiletin, a novel inhibitor, inhibits HBsAg production and hepatitis B virus replication
Zhongwen Hu1, Jieli Hu1, Fang Ren1
1The 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.
Insights
Nobiletin effectively reduces hepatitis B surface antigen (HBsAg) and HBV DNA in vitro and in vivo. This natural compound offers a promising new strategy for achieving a functional cure in chronic hepatitis B infection.
Area of Science:
- Hepatology
- Virology
- Drug Discovery
Background:
- Chronic hepatitis B virus (HBV) infection is a global health concern with severe outcomes like cirrhosis and liver cancer.
- Current treatments, including nucleos(t)ide analogs (NA) and PegIFN, often fail to achieve sustained loss of hepatitis B surface antigen (HBsAg), a key marker for functional cure.
- There is a critical need for novel therapeutic agents that can effectively target and reduce HBsAg levels.
Purpose of the Study:
- To identify and evaluate a new compound for its efficacy against chronic HBV infection, specifically targeting HBsAg reduction.
- To investigate the antiviral effects of nobiletin in both in vitro cell models and in vivo animal models.
- To assess the potential of nobiletin, alone and in combination with existing therapies, for improving HBV treatment outcomes.
Main Methods:
- Screening of 1500 compounds to identify nobiletin based on low cytotoxicity and high antiviral activity.
- In vitro assessment of nobiletin's effect on HBV in HepG2.2.15 and HepG2-NTCP cell lines.
- In vivo validation of nobiletin's antiviral capabilities in relevant animal models.
Main Results:
- Nobiletin demonstrated significant antiviral activity and low cytotoxicity.
- In vitro and in vivo studies showed that nobiletin effectively reduced both HBV DNA and HBsAg levels.
- Combination therapy with nobiletin and entecavir (ETV) resulted in substantial reductions in both HBV DNA and HBsAg.
Conclusions:
- Nobiletin emerges as a potent therapeutic candidate for chronic hepatitis B, effectively lowering both HBV DNA and HBsAg.
- This study highlights nobiletin's potential to overcome limitations of current therapies by targeting HBsAg for functional cure.
- Nobiletin represents a promising novel class of anti-HBV agents, potentially advancing the treatment landscape for hepatitis B infection.
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.
