An automated time-of-drug-addition assay to routinely determine the mode of action of HIV-1 inhibitors
Cell-based high-throughput screening campaigns are widely used to identify novel antiviral compounds, for example, against human immunodeficiency virus type 1 (HIV-1). Typically, these assays enable identification of compounds that potentially target any viral or cellular factor involved in the viral replication cycle. Unraveling the mechanism of action of these active compounds is an important step to facilitate further drug development. Time-of-addition (TOA) assays are an elegant tool to achieve this goal by comparing the TOA profile of novel compounds with those of well-studied reference compounds. Downscaling to a 384-well format and automation significantly increase the capacity of the TOA assay, enabling compound handling around the clock. Mechanical liquid dispensing with optimized time points for compound addition ensures robustness (Z'>0.8) and maximal resolution in profiling novel antiviral compounds. The presented methodology has been optimized for routine use and allows for fully automated high-throughput screening to support the process in search for novel inhibitors of HIV-1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Assay and drug development technologies - 11(2013), 8 vom: 03. Okt., Seite 489-500 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Van Loock, Marnix [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.05.2014 Date Revised 22.10.2013 published: Print Citation Status MEDLINE |
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| doi: |
10.1089/adt.2013.529 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM231871708 |
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| 520 | |a Cell-based high-throughput screening campaigns are widely used to identify novel antiviral compounds, for example, against human immunodeficiency virus type 1 (HIV-1). Typically, these assays enable identification of compounds that potentially target any viral or cellular factor involved in the viral replication cycle. Unraveling the mechanism of action of these active compounds is an important step to facilitate further drug development. Time-of-addition (TOA) assays are an elegant tool to achieve this goal by comparing the TOA profile of novel compounds with those of well-studied reference compounds. Downscaling to a 384-well format and automation significantly increase the capacity of the TOA assay, enabling compound handling around the clock. Mechanical liquid dispensing with optimized time points for compound addition ensures robustness (Z'>0.8) and maximal resolution in profiling novel antiviral compounds. The presented methodology has been optimized for routine use and allows for fully automated high-throughput screening to support the process in search for novel inhibitors of HIV-1 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Indicators and Reagents |2 NLM | |
| 700 | 1 | |a Van den Eynde, Christel |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, John |e verfasserin |4 aut | |
| 700 | 1 | |a Geluykens, Peggy |e verfasserin |4 aut | |
| 700 | 1 | |a Ivens, Tania |e verfasserin |4 aut | |
| 700 | 1 | |a Sauviller, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Bunkens, Lieve |e verfasserin |4 aut | |
| 700 | 1 | |a Van Acker, Koen |e verfasserin |4 aut | |
| 700 | 1 | |a Nijs, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Dams, Géry |e verfasserin |4 aut | |
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