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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 188-204
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.188
Naturally derived anti-hepatitis B virus agents and their mechanism of action
Yi-Hang Wu
Yi-Hang Wu, Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, Department of Pharmacy, College of Life Sciences, China Jiliang University, Hangzhou 310018, Zhejiang Province, China
Yi-Hang Wu, Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States
Author contributions: Wu YH designed and wrote the paper.
Supported by Zhejiang Provincial Natural Science Foundation of China, No. LY14H310010; Public Welfare Technology Applied Research Project of Zhejiang Province-Experimental Animal Science and Technology Project, No. 2013C37020; and Key Project of Chinese Ministry of Education, No. 212073.
Conflict-of-interest statement: The author has no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yi-Hang Wu, Professor, Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, Department of Pharmacy, College of Life Sciences, China Jiliang University, No. 258 Xueyuan Street, Hangzhou 310018, Zhejiang Province, China. yihangwu@126.com
Telephone: +86-571-86875676 Fax: +86-571-86914449
Received: May 28, 2015
Peer-review started: May 31, 2015
First decision: September 11, 2015
Revised: October 3, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 7, 2016
Processing time: 217 Days and 0.2 Hours
Abstract

Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus (HBV) are available for HBV patients, HBV infection is still a severe public health problem in the world. All the approved therapeutic drugs (including interferon-alpha and nucleoside analogues) have their limitations. No drugs or therapeutic methods can cure hepatitis B so far. Therefore, it is urgently needed to discover and develop new anti-HBV drugs, especially non-nucleoside agents. Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms. In this review, the natural products against HBV are discussed according to their chemical classes such as terpenes, lignans, phenolic acids, polyphenols, lactones, alkaloids and flavonoids. Furthermore, novel mode of action or new targets of some representative anti-HBV natural products are also discussed. The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20 years, especially novel skeletons and mode of action. Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date, scarcely any of them are found in the list of conventional anti-HBV drugs worldwide. Additionly, in anti-HBV mechanism of action, only a few references reported new targets or novel mode of action of anti-HBV natural products.

Keywords: Natural product; Hepatitis B virus; Structure; Mechanism of action; Drug target

Core tip: Hepatitis B virus (HBV) infection continues to be a significant health problem in the world. The urgent need for new anti-HBV drugs is a global concern. Naturally originated compounds with various skeletons and diverse biological activities provide a large reservoir for finding novel anti-HBV leads or candidates. In this review, the anti-HBV natural products are classified according to their structure types such as terpenes, lignans, phenolic acids, polyphenols, lactones, alkaloids and flavonoids. Furthermore, novel mode of action or new targets of some representative anti-HBV natural products are also discussed.