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Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.

ABSTRACT: 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 (EC50, EC90) 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 EC50. These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals.

SUBMITTER: Postnikova E

PROVIDER: S-EPMC5864066 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.

Postnikova Elena E Cong Yu Y DeWald Lisa Evans LE Dyall Julie J Yu Shuiqing S Hart Brit J BJ Zhou Huanying H Gross Robin R Logue James J Cai Yingyun Y Deiuliis Nicole N Michelotti Julia J Honko Anna N AN Bennett Richard S RS Holbrook Michael R MR Olinger Gene G GG Hensley Lisa E LE Jahrling Peter B PB

PloS one 20180322 3

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 ...[more]

PMID: 29566079

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Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.

Publications

Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.

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