Hepatitis B virus core protein (HBcAg) (HBcAg)

The Hepatitis B virus core protein (HBcAg) is a vital structural component of the Hepatitis B virus (HBV) responsible for the assembly of the viral nucleocapsid [1]. This protein self-assembles into an icosahedral shell that encapsulates the viral pregenomic RNA (pgRNA) and the viral polymerase, a process essential for the subsequent reverse transcription of the viral genome [2]. Beyond its structural role, HBcAg is involved in the intracellular transport of the viral genome to the host cell nucleus and the regulation of the covalently closed circular DNA (cccDNA) reservoir [3]. In chronic hepatitis B infection, the core protein is a major therapeutic target for a class of antivirals known as Capsid Assembly Modulators (CAMs) or Core protein Allosteric Modulators (CpAMs) [4]. These drugs bind to the core protein dimers and interfere with the assembly process, leading to either the formation of non-functional protein aggregates or the production of empty, genome-deficient capsids [3,5]. By inhibiting proper nucleocapsid formation and genome packaging, these therapies aim to significantly reduce viral replication and the replenishment of the cccDNA pool, potentially leading to a functional cure [2,4].

Other names

Hepatitis B virus core proteinHBV core proteinHepatitis B virus capsid proteinHBcp21cHepatitis B Virus nucleocapsid incorporation / viral particle assembly

Allosteric modulation of capsid assembly (Class I: induction of aberrant polymers; Class II: induction of empty capsids)