Antihepatitis B therapy: a review of current medications and novel small molecule inhibitors

• Published in: Fundamental & clinical pharmacology Vol. 28; no. 4; pp. 364 - 381
• Main Authors: Qiu, Li-Peng, Chen, Liang, Chen, Ke-Ping
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.08.2014; Blackwell
• Subjects: Animals; anti-HBV activity; Antiviral Agents - adverse effects; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Carcinoma, Hepatocellular - prevention & control; Carcinoma, Hepatocellular - virology; Drug Approval; Drug Design; Hepatitis B virus; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - epidemiology; Humans; Liver Cirrhosis - prevention & control; Liver Cirrhosis - virology; Liver Neoplasms - prevention & control; Liver Neoplasms - virology; mechanism of action; Medical sciences; non-nucleos(t)ide analogs; nucleos(t)ide analogs; Pharmacology. Drug treatments; Drug; non-nucleos(t)ide analogs; nucleos(t)ide analogs; Orthohepadnavirus; Review; Biological activity; Virus; Treatment; Hepadnaviridae; Analog; anti-HBV activity; Inhibitor; Small molecule; Hepatitis B virus; Mechanism of action; Bibliographic review; mechanism of action; hepatitis B virus
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12053

There are approximately 350 million hepatitis B virus (HBV) carriers worldwide. Chronic HBV infection increases the risk of liver cirrhosis and hepatocellular carcinoma. To date, two classes of antiviral drugs have been approved by the Food and Drug Administration for the treatment of hepatitis B, immunomodulators (interferon [IFN]‐α and pegylated‐interferon [PEG‐IFN]‐α) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV]). Of these, ETV, TDF, and PEG‐IFN‐α are the most effective and are currently recommended for anti‐HBV therapy. However, these therapies are less than optimal because of their low rate of viral DNA and surface antigen clearance; thus, there exists a significant unmet medical need for safe and efficacious new anti‐HBV drugs. Covering diverse chemical structures and mechanisms of action, non‐nucleos(t)ide compounds offer great promise in the search for new anti‐HBV drugs. This review summarizes the currently approved anti‐HBV drugs and highlights advances in the identification and characterization of novel small molecule HBV inhibitors. We discuss the sources, structures, anti‐HBV effects, mechanisms of action, and potential toxicities of these novel inhibitors.