Virus Assembly Antagonists from Redesigned Antibodies

Abstract

There is no reliable cure for chronic Hepatitis B Virus (HBV). In this issue of Structure, Eren et al. (2018) show how antibody-derived proteins bind different forms of the HBV capsid protein, blocking assembly. This interaction may also affect downstream signaling. These antibody-derived molecules mark a new strategy that may ultimately contribute to a cure.

Figure 1.. Dimeric Forms of the HBV Core Gene Products

(A) The capsid (HBcAg) conformation has a spike at the intradimer interface formed by helices 3 and 4 from both monomers. Helix 5 and the following sequence form the interdimer interface. (B) A comparison of HBcAg from capsid (orange, 1QGT), the older HBeAg structure (blue, 3V6Z), and the new HBeAg dimer (cyan, 6CVK). The three structures are aligned based on one monomer; the other halves of the dimers are in substantially different positions. (C) An HBcAg dimer with a molecular surface highlighting the epitopes bound by FAB e21 (red) and scFV e13 (blue) (see table S1 in Eren et al. (2018)). Both epitopes include helix 5 and are distal to the major epitope of HBcAg, the tip of the spike. (D) Two HBcAg dimers, extracted from a capsid, interact via contacts with helix 5. These interactions occlude e13 and e21 epitopes.