Abstract
Hepatitis B virus (HBV) is a major causative agent of human hepatitis. Its viral genome comprises partially double-stranded DNA, which is complexed with viral polymerase within an icosahedral capsid consisting of a dimeric core protein. Here, we describe the effects of capsid assembly modulators (CAMs) on the geometric or kinetic disruption of capsid construction and the virus life cycle. We highlight classical, early-generation CAMs such as heteroaryldihydropyrimidines, phenylpropenamides or sulfamoylbenzamides, and focus on the chemical structure and antiviral efficacy of recently identified non-classical CAMs, which consist of carboxamides, aryl ureas, bithiazoles, hydrazones, benzylpyridazinones, pyrimidines, quinolines, dyes, and antimicrobial compounds. We summarize the therapeutic efficacy of four representative classical compounds with data from clinical phase 1 studies in chronic HBV patients. Most of these compounds are in phase 2 trials, either as monotherapy or in combination with approved nucleos(t)ides drugs or other immunostimulatory molecules. As followers of the early CAMs, the therapeutic efficacy of several non-classical CAMs has been evaluated in humanized mouse models of HBV infection. It is expected that these next-generation HBV CAMs will be promising candidates for a series of extended human clinical trials.
Highlights
Hepatitis B virus (HBV) is a common, contagious liver infection that spreads from human to human through blood, body fluids, or perinatally [1]
The HBV core protein is involved in almost every step of the HBV life cycle
As a multiplayer in the HBV life cycle, the core protein is an attractive target for direct-acting antivirals
Summary
Hepatitis B virus (HBV) is a common, contagious liver infection that spreads from human to human through blood, body fluids, or perinatally [1]. HBV is a severe global public health burden, with high endemicity levels in sub-Saharan Africa and East Asian countries [2] Both acute and chronic HBV infections are primarily diagnosed by the serological levels of viral surface antigen (HBsAg), while acute or recently acquired HBV infections are determined by the presence of immunoglobulin M antibody to viral core antigen (IgM anti-HBcAg) [3]. These aim to achieve a functional cure accompanied by the clinical outcomes of HBeAg and/or HBsAg seroconversion and removal of HBV DNA/RNA without the need for lifelong drug administration. We will focus on the chemical structure and antiviral efficacy of the most recently identified non-classical CAMs, and outline the current progress of clinical efficacy studies of classical CAMs, either as monotherapy or in combination with other drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
