Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.
Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs.
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DOI：
10.1371/journal.pone.0194880
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Jahrling PB
中科院分区：
文献类型：
--
作者：
Postnikova E;Cong Y;DeWald LE;Dyall J;Yu S;Hart BJ;Zhou H;Gross R;Logue J;Cai Y;Deiuliis N;Michelotti J;Honko AN;Bennett RS;Holbrook MR;Olinger GG;Hensley LE;Jahrling PB
确定治疗埃博拉病毒病（EVD）的有效抗病毒药物并最大限度地减少此类疾病的传播至关重要。已经开发了多种基于细胞的测定来评估化合物针对埃博拉病毒的活性。然而，很少有报告讨论可变的测定条件，可以影响从这些药物筛选获得的结果。在这里，我们描述了在开发基于细胞的药物筛选试验期间测试的可变条件，该试验旨在使用已建立的细胞系和人原代细胞鉴定具有抗埃博拉病毒活性的化合物。比较了多个试验读数和可变试验条件（包括病毒输入、感染时间和细胞传代次数）的影响，并使用FDA批准的化合物枸橼酸托瑞米芬评价了对50%和/或90%抑制有效浓度（EC 50、EC 90）的影响。在这些研究中，我们表明，改变基于细胞的测定条件可能会对通过EC 50测量的表观药物效力产生影响。这些结果进一步支持了制定标准操作规程以生成可靠且可重现的潜在抗病毒药物体外数据集的重要性。
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.
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影响因子：
1.1
作者：
Gerken, Patty
通讯作者：
Gerken, Patty
DOI：
10.1074/jbc.m110.207084
发表时间：
2011-05-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Miller EH;Harrison JS;Radoshitzky SR;Higgins CD;Chi X;Dong L;Kuhn JH;Bavari S;Lai JR;Chandran K
通讯作者：
Chandran K
影响因子：
6.4
作者：
Basu, Arnab;Mills, Debra M.;Bowlin, Terry L.
通讯作者：
Bowlin, Terry L.
影响因子：
9.4
作者：
Drosten, C;Göttig, S;Günther, S
通讯作者：
Günther, S
影响因子：
7.6
作者：
Panchal, Rekha G.;Reid, St. Patrick;Bavari, Sina
通讯作者：
Bavari, Sina