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Inhibitors of SARS-CoV entry - Identification using an internally-controlled dual envelope pseudovirion assay

Identifieur interne : 002370 ( Main/Curation ); précédent : 002369; suivant : 002371

Inhibitors of SARS-CoV entry - Identification using an internally-controlled dual envelope pseudovirion assay

Auteurs : Yanchen Zhou [États-Unis] ; Juliet Agudelo [États-Unis] ; Kai Lu [États-Unis] ; David H. Goetz [États-Unis] ; Elizabeth Hansell [États-Unis] ; Yen Ting Chen [États-Unis] ; William R. Roush [États-Unis] ; James Mckerrow [États-Unis] ; Charles S. Craik [États-Unis] ; Sean M. Amberg [États-Unis] ; Graham Simmons [États-Unis]

Source :

RBID : Pascal:12-0002103

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English descriptors

Abstract

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.

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Pascal:12-0002103

Le document en format XML

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<term>Antiviral</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Drug Evaluation, Preclinical (methods)</term>
<term>Drug Evaluation, Preclinical (standards)</term>
<term>Envelope</term>
<term>High throughput screening</term>
<term>High-Throughput Screening Assays (methods)</term>
<term>High-Throughput Screening Assays (standards)</term>
<term>Humans</term>
<term>Identification</term>
<term>Inhibitor</term>
<term>Microbial Sensitivity Tests (methods)</term>
<term>Microbial Sensitivity Tests (standards)</term>
<term>Performance evaluation</term>
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<term>Severe acute respiratory syndrome virus</term>
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<term>Antiviraux (pharmacologie)</term>
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<term>Tests de criblage à haut débit (normes)</term>
<term>Tests de sensibilité microbienne ()</term>
<term>Tests de sensibilité microbienne (normes)</term>
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<title xml:lang="en" level="a" type="main">Inhibitors of SARS-CoV entry – Identification using an internally-controlled dual envelope pseudovirion assay</title>
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<name sortKey="Zhou, Yanchen" sort="Zhou, Yanchen" uniqKey="Zhou Y" first="Yanchen" last="Zhou">Yanchen Zhou</name>
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<name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name>
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<name sortKey="Goetz, David H" sort="Goetz, David H" uniqKey="Goetz D" first="David H." last="Goetz">David H. Goetz</name>
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<region type="state">Oregon</region>
</placeName>
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<title level="j">Antiviral Research</title>
<idno type="ISSN">0166-3542</idno>
<idno type="eISSN">1872-9096</idno>
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<date when="2011">2011</date>
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<term>Antiviral Agents (pharmacology)</term>
<term>Drug Evaluation, Preclinical (methods)</term>
<term>Drug Evaluation, Preclinical (standards)</term>
<term>High-Throughput Screening Assays (methods)</term>
<term>High-Throughput Screening Assays (standards)</term>
<term>Humans</term>
<term>Microbial Sensitivity Tests (methods)</term>
<term>Microbial Sensitivity Tests (standards)</term>
<term>SARS Virus (drug effects)</term>
<term>Virus Cultivation (methods)</term>
<term>Virus Cultivation (standards)</term>
<term>Virus Internalization (drug effects)</term>
</keywords>
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<term>Antiviraux (pharmacologie)</term>
<term>Culture virale ()</term>
<term>Culture virale (normes)</term>
<term>Humains</term>
<term>Pénétration virale ()</term>
<term>Tests de criblage à haut débit ()</term>
<term>Tests de criblage à haut débit (normes)</term>
<term>Tests de sensibilité microbienne ()</term>
<term>Tests de sensibilité microbienne (normes)</term>
<term>Virus du SRAS ()</term>
<term>Évaluation préclinique de médicament ()</term>
<term>Évaluation préclinique de médicament (normes)</term>
</keywords>
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<term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>SARS Virus</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en">
<term>Drug Evaluation, Preclinical</term>
<term>High-Throughput Screening Assays</term>
<term>Microbial Sensitivity Tests</term>
<term>Virus Cultivation</term>
</keywords>
<keywords scheme="MESH" qualifier="normes" xml:lang="fr">
<term>Culture virale</term>
<term>Tests de criblage à haut débit</term>
<term>Tests de sensibilité microbienne</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antiviraux</term>
</keywords>
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<term>Drug Evaluation, Preclinical</term>
<term>High-Throughput Screening Assays</term>
<term>Microbial Sensitivity Tests</term>
<term>Virus Cultivation</term>
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<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Culture virale</term>
<term>Humains</term>
<term>Pénétration virale</term>
<term>Tests de criblage à haut débit</term>
<term>Tests de sensibilité microbienne</term>
<term>Virus du SRAS</term>
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<div type="abstract" xml:lang="en">
<title>Highlights</title>
<p>► We describe a novel assay for screening inhibitors of viral entry. ► The inclusion of an internal control envelope controls for specificity. ► This assay system can be adapted for most enveloped viruses. ► Examples of screens for inhibitors of SARS-CoV entry were performed. ► A number of compounds were identified that inhibit SARS-CoV entry and replication.</p>
</div>
</front>
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