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

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 cap...

Full description

Saved in:
Bibliographic Details
Published inAntimicrobial agents and chemotherapy Vol. 62; no. 12
Main Authors Wei, Xia-Fei, Gan, Chun-Yang, Cui, Jing, Luo, Ying-Ying, Cai, Xue-Fei, Yuan, Yi, Shen, Jing, Li, Zhi-Ying, Zhang, Wen-Lu, Long, Quan-Xin, Hu, Yuan, Chen, Juan, Tang, Ni, Guo, Haitao, Huang, Ai-Long, Hu, Jie-Li
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.12.2018
Subjects
Antiviral Agents
Diterpenes
Gene Expression Regulation, Viral
Hepatitis B virus
Indoles
Protein Multimerization
Viral Core Proteins
split luciferase
hepatitis B virus
dimer
20-deoxyingenol
core protein
Arbidol
compound screen
cell model
Online AccessGet full text

Cover

More Information
Summary: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. 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
X.-F.W., C.-Y.G., and J.C. contributed equally to this work.
Citation Wei X-F, Gan C-Y, Cui J, Luo Y-Y, Cai X-F, Yuan Y, Shen J, Li Z-Y, Zhang W-L, Long Q-X, Hu Y, Chen J, Tang N, Guo H, Huang A-L, Hu J-L. 2018. Identification of compounds targeting hepatitis B virus core protein dimerization through a split luciferase complementation assay. Antimicrob Agents Chemother 62:e01302-18. https://doi.org/10.1128/AAC.01302-18.
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/AAC.01302-18