Core Protein-Directed Antivirals and Importin β Can Synergistically Disrupt Hepatitis B Virus Capsids
Christine Kim, Lauren F. Barnes, Christopher J. Schlicksup, Angela J. Patterson, Brian Bothner, Martin F. Jarrold, Joseph Che‐Yen Wang, Adam Zlotnick
Abstract
The HBV core, an icosahedral complex of 120 copies of the homodimeric core (capsid) protein with or without packaged nucleic acid, is transported to the host nucleus by its interaction with host importin proteins. Importin-core interaction requires the core protein C-terminal domain, which is inside the capsid, to "flip" to the capsid exterior. Core protein-directed drugs that affect capsid assembly and stability have been developed recently. We show that these molecules can, synergistically with importins, disrupt capsids. This mechanism of action, synergism with host protein, has the potential to disrupt the virus life cycle and activate the innate immune system.