Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure

• Type of Material: Article
• Authors: William McFadden, Emory University; Stefan Sarafianos, Emory University
• Language: English
• Date: 2023-08-31
• Publisher: National Center for Global Health and Medicine
• Publication Version: Final Published Version
• Copyright Statement: 2023, National Center for Global Health and Medicine
• Final Published Version (URL): https://doi.org/10.35772%2Fghm.2023.01065
• Title of Journal or Parent Work: Global Health & Medicine
• Volume: 5
• Issue: 4
• Start Page: 199
• End Page: 207
• Grant/Funding Information: This research was supported in part by the National Institutes of Health (R01 AI132833 and R01 AI121315 to SGS; WMM was supported in part by T32 GM135060 and F31 AI174951). SGS acknowledges funding from the Nahmias-Schinazi Distinguished Chair in Research.
• Keywords: HBV; global health problem; hepadnaviridae; hepatitis; covalently closed chromosomal DNA (cccDNA); capsid assembly modulators (CAMs); capsid core; HBV surface antigen (HBsAg)
• Research Categories: Health Sciences, Public Health; Biology, Genetics; Biology, Virology

Abstract

Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.