Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization through a Split Luciferase Complementation Assay

Antimicrobial Agents and Chemotherapy
Xia-Fei WeiJie-Li Hu

Abstract

The capsid of the hepatitis B virus is an attractive antiviral target for developing therapies against chronic hepatitis B infection. 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, namely, 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 here a cell-based assay in which the formation of core dimers is indicated by split luciferase complementation (SLC). Making use of this model, 2 compounds, Arbidol (umifenovir) and 20-deoxyingenol, were identified from a library containing 672 compounds as core dimerization regulators. Arbidol and 20-deoxyingenol inhibit the hepatitis B virus (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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Citations

Feb 13, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Taha AzadJohn C Bell
Mar 18, 2021·Immune Network·Erica EspañoJeong-Ki Kim
Aug 5, 2021·Immunity, Inflammation and Disease·Behnam AmaniMahsa Zareei
Sep 18, 2021·Biomedical Chromatography : BMC·Jing-Ze LuBing-Liang Ma

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