Novel cell-based hepatitis C virus infection assay for quantitative high-throughput screening of anti-hepatitis C virus compounds

Zongyi Hu, Keng Hsin Lan, Shanshan He, Manju Swaroop, Xin Hu, Noel Southall, Wei Zheng, T. Jake Liang

Research output: Contribution to journalArticlepeer-review

Abstract

Therapy for hepatitis C virus (HCV) infection has advanced with the recent approval of direct-acting antivirals in combination with peginterferon and ribavirin. New antivirals with novel targets are still needed to further improve the treatment of hepatitis C. Previously reported screening methods for HCV inhibitors either are limited to a virus-specific function or apply a screening method at a single dose, which usually leads to high false-positive or -negative rates. We developed a quantitative high-throughput screening (qHTS) assay platform with a cell-based HCV infection system. This highly sensitive assay can be miniaturized to a 1,536-well format for screening of large chemical libraries. All candidates are screened over a 7-concentration dose range to give EC50s (compound concentrations at 50% efficacy) and dose-response curves. Using this assay format, we screened a library of pharmacologically active compounds (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and cytotoxicity, 22 compounds with adequate curves and EC50s of70% and CC50s (compound concentrations at 50% cytotoxicity) of

Original languageEnglish (US)
Pages (from-to)995-1004
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

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