Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization through a Split Luciferase Complementation Assay
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.
References
NanoLuc Complementation Reporter Optimized for Accurate Measurement of Protein Interactions in Cells
Citations
Related Concepts
Related Feeds
CRISPR Screens in Drug Resistance
CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.
Antivirals
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.
Antivirals (ASM)
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.