Development of a homogeneous screening assay for automated detection of antiviral agents active against severe acute respiratory syndrome-associated coronavirus.
Identifieur interne : 004B74 ( Main/Merge ); précédent : 004B73; suivant : 004B75Development of a homogeneous screening assay for automated detection of antiviral agents active against severe acute respiratory syndrome-associated coronavirus.
Auteurs : Tania Ivens [Belgique] ; Christel Van Den Eynde ; Koen Van Acker ; Erik Nijs ; Géry Dams ; Eva Bettens ; Asa Ohagen ; Rudi Pauwels ; Kurt HertogsSource :
- Journal of virological methods [ 0166-0934 ] ; 2005.
Descripteurs français
- KwdFr :
- MESH :
- analyse : Antiviraux.
- métabolisme : Antiviraux.
- pharmacologie : Antiviraux.
- physiologie : Virus du SRAS.
- Antiviraux, Lignée cellulaire, Protéines à fluorescence verte, Réplication virale, Virus du SRAS, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- MESH :
- chemical , analysis : Antiviral Agents.
- chemical , chemistry : Antiviral Agents.
- chemical , metabolism : Antiviral Agents.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS Virus, Virus Replication.
- physiology : SARS Virus.
- Cell Line, Drug Evaluation, Preclinical, Green Fluorescent Proteins.
Abstract
The severity and global spread of the 2003 outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlighted the risks to human health posed by emerging viral diseases and emphasized the need for specific therapeutic agents instead of relying on existing broadly active antiviral compounds. The development of rapid screening assays is essential for antiviral drug discovery. Thus, a screening system for anti-SARS-CoV agents was developed, which evaluated compound potency, specificity and cytotoxicity at the initial screening phase. Cell lines were engineered to constitutively express an enhanced green fluorescent protein (EGFP) and used to detect (1) antiviral potency in SARS-CoV infection tests; (2) antiviral specificity in tests using the porcine coronavirus transmissible gastroenteritis virus (TGEV); and (3) cytotoxicity in the same assays without virus challenge. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. The suitability of this assay system in drug discovery was demonstrated by screening of 3388 small molecule compounds. The results show that these assays can be applied to high-throughput screening for identification of inhibitors selectively active against SARS-CoV.
DOI: 10.1016/j.jviromet.2005.05.010
PubMed: 15961169
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pubmed:15961169Le document en format XML
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<term>Drug Evaluation, Preclinical</term>
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<term>SARS Virus (physiology)</term>
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<front><div type="abstract" xml:lang="en">The severity and global spread of the 2003 outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlighted the risks to human health posed by emerging viral diseases and emphasized the need for specific therapeutic agents instead of relying on existing broadly active antiviral compounds. The development of rapid screening assays is essential for antiviral drug discovery. Thus, a screening system for anti-SARS-CoV agents was developed, which evaluated compound potency, specificity and cytotoxicity at the initial screening phase. Cell lines were engineered to constitutively express an enhanced green fluorescent protein (EGFP) and used to detect (1) antiviral potency in SARS-CoV infection tests; (2) antiviral specificity in tests using the porcine coronavirus transmissible gastroenteritis virus (TGEV); and (3) cytotoxicity in the same assays without virus challenge. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. The suitability of this assay system in drug discovery was demonstrated by screening of 3388 small molecule compounds. The results show that these assays can be applied to high-throughput screening for identification of inhibitors selectively active against SARS-CoV.</div>
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