(A & B). HBV replication mechanism and schematic representation of
CAM-modulations sites. Panel A represents the HBV particle, and panel B
represents the different steps of the HBV replication being affected by CAMs.
The dotted arrows in red represent the effects of CAMs on (i) the nuclear
transfer of relaxed circular (RC) DNA containing nucleocapsid for covalently
closed circular DNA (cccDNA) synthesis and cccDNA recycling/amplification, (ii)
core protein (Cp) secretion on plasma or cytoplasm for nucleocapsid assembly,
and nuclear transfer for cccDNA formation, (iii) capsid assembly for pre-genomic
RNA (pgRNA) encapsidation, (iv) inhibition of reverse transcription to
single-stranded (SS) DNA, (v) HBeAg secretion, and (vi) exposure of HBV DNA for
integration in the host genome with low levels of HBsAg production. S, small, M,
medium, L, large hepatitis B surface (HBs); DS, double stranded; NTCP, sodium
taurocholate co-transporting polypeptide; CAM, capsid assembly modulator.