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

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.

Dopamine Inhibits the Expression of Hepatitis B Virus Surface and e Antigens by Activating the JAK/STAT Pathway and Upregulating Interferon-stimulated Gene 15 Expression

“…However, these drug candidates are still in preclinical or early clinical stages of development. 45 , 46 …”

“…However, these drug candidates are still in preclinical or early clinical stages of development. 45,46 In this study, we investigated the antiviral activity of dopamine, a small molecule compound. Our findings demonstrate that dopamine substantially reduced the level of HBV DNA, which was consistent with our previous study showing that dopamine reduced HBV DNA replication by inhibiting the binding of ε RNA with the HBV polymerase.…”

Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen

“…Capsid assembly modulators (CAMs) targeting the core region have been shown to suppress pregenomic RNA and reduce cccDNA [101,102]. CAMs are expected to be novel therapeutic agents against HBV [103][104][105][106][107]. It is hoped that knowledge of the HBV core region will continue to increase in the future.…”