Development of a homogeneous screening assay for automated detection of antiviral agents active against severe acute respiratory syndrome-associated coronavirus
Identifieur interne : 004E41 ( Main/Curation ); précédent : 004E40; suivant : 004E42Development 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 [Belgique] ; Koen Van Acker [Belgique] ; Erik Nijs [Belgique] ; Géry Dams [Belgique] ; Eva Bettens [Belgique] ; Asa Ohagen [Belgique] ; Rudi Pauwels [Belgique] ; Kurt Hertogs [Belgique]Source :
- Journal of virological methods [ 0166-0934 ] ; 2005.
Descripteurs français
- KwdFr :
- MESH :
- analyse : Antiviraux.
- métabolisme : Antiviraux.
- pharmacologie : Antiviraux.
- physiologie : Virus du SRAS.
- Pascal (Inist)
English descriptors
- KwdEn :
- Antiviral, Antiviral Agents (analysis), Antiviral Agents (chemistry), Antiviral Agents (metabolism), Antiviral Agents (pharmacology), Cell Line, Coronavirus, Detection, Drug Evaluation, Preclinical, Green Fluorescent Proteins, High throughput screening, Method, Microbiology, SARS Virus (drug effects), SARS Virus (physiology), Severe acute respiratory syndrome, Virology, Virus Replication (drug effects).
- 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 (I) 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.
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Pascal:05-0419019Le document en format XML
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<term>Antiviral Agents (analysis)</term>
<term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (metabolism)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line</term>
<term>Coronavirus</term>
<term>Detection</term>
<term>Drug Evaluation, Preclinical</term>
<term>Green Fluorescent Proteins</term>
<term>High throughput screening</term>
<term>Method</term>
<term>Microbiology</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (physiology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Virology</term>
<term>Virus Replication (drug effects)</term>
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<term>Antiviraux (analyse)</term>
<term>Antiviraux (métabolisme)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Lignée cellulaire</term>
<term>Protéines à fluorescence verte</term>
<term>Réplication virale ()</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (physiologie)</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Antiviral Agents</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 (I) 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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<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 (I) 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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<affiliation wicri:level="1"><nlm:affiliation>Tibotec BVBA, Lead Discovery Operations, Gen De Wittelaan L 11B 3, Mechelen 2800, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Tibotec BVBA, Lead Discovery Operations, Gen De Wittelaan L 11B 3, Mechelen 2800</wicri:regionArea>
<wicri:noRegion>Mechelen 2800</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Den Eynde, Christel" sort="Van Den Eynde, Christel" uniqKey="Van Den Eynde C" first="Christel" last="Van Den Eynde">Christel Van Den Eynde</name>
</author>
<author><name sortKey="Van Acker, Koen" sort="Van Acker, Koen" uniqKey="Van Acker K" first="Koen" last="Van Acker">Koen Van Acker</name>
</author>
<author><name sortKey="Nijs, Erik" sort="Nijs, Erik" uniqKey="Nijs E" first="Erik" last="Nijs">Erik Nijs</name>
</author>
<author><name sortKey="Dams, Gery" sort="Dams, Gery" uniqKey="Dams G" first="Géry" last="Dams">Géry Dams</name>
</author>
<author><name sortKey="Bettens, Eva" sort="Bettens, Eva" uniqKey="Bettens E" first="Eva" last="Bettens">Eva Bettens</name>
</author>
<author><name sortKey="Ohagen, Asa" sort="Ohagen, Asa" uniqKey="Ohagen A" first="Asa" last="Ohagen">Asa Ohagen</name>
</author>
<author><name sortKey="Pauwels, Rudi" sort="Pauwels, Rudi" uniqKey="Pauwels R" first="Rudi" last="Pauwels">Rudi Pauwels</name>
</author>
<author><name sortKey="Hertogs, Kurt" sort="Hertogs, Kurt" uniqKey="Hertogs K" first="Kurt" last="Hertogs">Kurt Hertogs</name>
</author>
</analytic>
<series><title level="j">Journal of virological methods</title>
<idno type="ISSN">0166-0934</idno>
<imprint><date when="2005" type="published">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (analysis)</term>
<term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (metabolism)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line</term>
<term>Drug Evaluation, Preclinical</term>
<term>Green Fluorescent Proteins</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (physiology)</term>
<term>Virus Replication (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux ()</term>
<term>Antiviraux (analyse)</term>
<term>Antiviraux (métabolisme)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Lignée cellulaire</term>
<term>Protéines à fluorescence verte</term>
<term>Réplication virale ()</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (physiologie)</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Line</term>
<term>Drug Evaluation, Preclinical</term>
<term>Green Fluorescent Proteins</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Antiviraux</term>
<term>Lignée cellulaire</term>
<term>Protéines à fluorescence verte</term>
<term>Réplication virale</term>
<term>Virus du SRAS</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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>
</front>
</TEI>
</PubMed>
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