Figure 8. A Schematic of Viral Replication Pathways that can Potentially be Inhibited by Fab/scFv or Mab Forms of e13 and e21.

(A) Inhibition of HBcAg_c assembly in the cytoplasm. The scheme shows that antibody fragments e13 and e21 can bind to transiently existing HBcAg_d before they can assemble into HBcAg_c in the cytoplasm, which in turn can block the downstream formation of infectious Dane particles, preventing transport of the viral genome and infection of healthy cells. (B) Inhibition of HBeAg_c assembly in the cytoplasm. Cell-penetrating antibody fragments of e13 and e21 can bind to reduced HBeAg_d, preventing its conversion into the HBcAg_d-like arrangement (left), or binding to any HBeAg_d that has already converted to the assembly competent arrangement, blocking the assembly of decoy particles (right). (C) Inhibition of cytoplasmic HBeAg_d-mediated immune-modulation by binding to HBeAg and blocking its interaction with host proteins such as Mal and TRAM. (D) Inhibition of circulating HBeAg_d-mediated immune-modulation by binding of Mab versions of e13 and e21, which could trigger clearance of HBeAg through antibody-dependent mechanisms. In this scheme, HBcAg_d and HBeAg_d are represented as gray cartoons and antibody fragments as magenta cartoons. Disulfide bonds are represented by yellow lines while the non-bonded Cys residues are shown as yellow dots. The PP is represented by a red undulating line. Red crosses on blue arrows indicate pathways that can potentially be inhibited by antibody fragments.