Open AccessTesting therapeutics in cell-based assays: Factors that influence the apparent potency of drugs
Author(s) -
Elena Postnikova,
Cong Yu,
Lisa Evans DeWald,
Julie Dyall,
Shuǐqìng Yú,
Brit J. Hart,
Huanying Zhou,
Robin Gross,
James Logue,
Yíngyún Caì,
Nicole Deiuliis,
Julia Michelotti,
An. Honko,
Richard S. Bennett,
Michael R. Holbrook,
Gene G. Olinger,
Lisa E. Hensley,
Peter B. Jahrling
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0194880
Subject(s) - potency , ebola virus , ec50 , drug , virus , pharmacology , cell , drug discovery , in vitro toxicology , bioassay , virology , in vitro , biology , bioinformatics , biochemistry , genetics
Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such disease is critical. A variety of cell-based assays have been developed for evaluating compounds for activity against Ebola virus. However, very few reports discuss the variable assay conditions that can affect the results obtained from these drug screens. Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC 50 , EC 90 ) was evaluated using the FDA-approved compound, toremifene citrate. In these studies, we show that altering cell-based assay conditions can have an impact on apparent drug potency as measured by the EC 50 . These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals.