Logo image
Back
Screening and identification of compounds with antiviral activity against hepatitis B virus using a safe compound library and novel real-time immune-absorbance PCR-based high throughput system
Journal article   Open access   Peer reviewed

Screening and identification of compounds with antiviral activity against hepatitis B virus using a safe compound library and novel real-time immune-absorbance PCR-based high throughput system

Jason Lamontagne, Courtney Mills, Richeng Mao, Cally Goddard, Dawei Cai, Haitao Guo, Andy Cuconati, Timothy Block and Xuanyong Lu
Antiviral research, v 98(1), pp 19-26
Apr 2013
DOI: https://doi.org/10.1016/j.antiviral.2013.02.001
PMID: 23415884
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc3628437View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Antiviral drug Chlorophyllide Hepatitis B virus Immune-absorbance polymerase chain reaction Polymerase chain reaction Proparacaine
► A high throughput screening system utilizing a novel immune-absorbance qPCR assay was established. ► Using this system, 2000 compounds with known safety profiles were screened for activity against HBV. ► Eight compounds were shown to have anti-hepatitis B virus (HBV) activity. ► The anti-HBV mechanism of proparacaine and chlorophyllide has been further studied. There are now seven nucleoside/tide analogues, along with interferon-α, that are approved by the FDA for the management of chronic hepatitis B virus (HBV) infection, a disease affecting hundreds of millions of people worldwide. These medications, however, are limited in usefulness, and significant side effects and the emergence of viral escape mutants make the development of novel and updated therapeutics a pressing need in the treatment of HBV. With this in mind, a library containing 2000 compounds already known to be safe in both humans and mice with known mechanisms of action in mammalian cells were tested for the possibility of either antiviral activity against HBV or selective toxicity in HBV producing cell lines. A modified real-time immune-absorbance-polymerase chain reaction (IA-PCR) assay was developed for this screen, utilizing cells that produce and secrete intact HBV virions. In this procedure, viral particles are first captured by an anti-HBs antibody immobilized on a plate. The viral load is subsequently assessed by real-time PCR directly on captured particles. Using this assay, eight compounds were shown to consistently reduce the amount of secreted HBV viral particles in the culture medium under conditions that had no detectable impact on cell viability. Two compounds, proparacaine and chlorophyllide, were shown to reduce HBV levels 4- to 6-fold with an IC50 of 1 and 1.5μM, respectively, and were selected for further study. The identification of these compounds as promising antiviral drug candidates against HBV, despite a lack of previous recognition of HBV antiviral activity, supports the validity and utility of testing known compounds for “off-pathogen target” activity against HBV, and also validates this IA-PCR assay as an important tool for the detection of anti-viral activity against enveloped viruses.

Metrics

11 Record Views
14 citations in Web of Science
14 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Pharmacology & Pharmacy
Virology
Logo image