Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization Through a Split Luciferase Complementation Assay [Antiviral Agents]

The capsid of hepatitis B virus is an attractive antiviral target for developing therapies against chronic hepatitis B. Currently available core protein allosteric modulators (CpAMs) mainly affect one of the two major types of protein-protein interactions involved in the process of capsid assembly, which is the interaction between the core dimers. Compounds targeting the interaction between two core monomers have not been rigorously screened due to the lack of screening models. We report herein a cell-based assay in which the formation of core dimers is indicated by the Split Luciferase Complementation (SLC). Making use of this model, 2 compounds, Arbidol and 20-Deoxyingenol, were identified as core dimerization regulators from a library containing 672 compounds. Arbidol and 20-Deoxyingenol inhibit the HBV DNA replication in vitro by decreasing and increasing the formation of core dimer and capsid, respectively. Our results provided a proof of concept for the cell model to be used to screen new agents targeting the step of core dimer and capsid formation.

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