Antimicrob Agents Chemother. 2018 Sep 17. pii: AAC.01302-18. doi: 10.1128/AAC.01302-18. [Epub ahead of print]
Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization Through a Split Luciferase Complementation Assay.
Wei XF1,2, Gan CY1, Cui J1, Luo YY1, Cai XF1, Yuan Y1, Shen J1, Li ZY, Zhang WL1, Long QX1, Hu Y1, Chen J1, Tang N1, Guo H3, Huang AL4,2, Hu JL4,2.
Author information
1
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
2
Collaborative Innovation Center for diagnosis and treatment of infectious diseases (CCID), Hangzhou, China.
3
Department of Microbiology and Immunology, Indiana University School of Medicine.
4
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China [email protected][email protected].
Abstract
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.