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

Identifieur interne : 002370 ( Main/Exploration ); 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

Descripteurs français

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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Le document en format XML

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<term>High-Throughput Screening Assays (methods)</term>
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<term>Virus Cultivation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Humans</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Culture virale</term>
<term>Humains</term>
<term>Inhibiteur</term>
<term>Pénétration virale</term>
<term>Tests de criblage à haut débit</term>
<term>Tests de sensibilité microbienne</term>
<term>Virus du SRAS</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Identification</term>
<term>Enveloppe</term>
<term>Pseudovirion</term>
<term>Antiviral</term>
<term>Criblage haut débit</term>
<term>Evaluation performance</term>
<term>Technique</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Floride</li>
<li>Oregon</li>
</region>
</list>
<tree>
<country name="États-Unis">
<region name="Californie">
<name sortKey="Zhou, Yanchen" sort="Zhou, Yanchen" uniqKey="Zhou Y" first="Yanchen" last="Zhou">Yanchen Zhou</name>
</region>
<name sortKey="Agudelo, Juliet" sort="Agudelo, Juliet" uniqKey="Agudelo J" first="Juliet" last="Agudelo">Juliet Agudelo</name>
<name sortKey="Amberg, Sean M" sort="Amberg, Sean M" uniqKey="Amberg S" first="Sean M." last="Amberg">Sean M. Amberg</name>
<name sortKey="Chen, Yen Ting" sort="Chen, Yen Ting" uniqKey="Chen Y" first="Yen Ting" last="Chen">Yen Ting Chen</name>
<name sortKey="Craik, Charles S" sort="Craik, Charles S" uniqKey="Craik C" first="Charles S." last="Craik">Charles S. Craik</name>
<name sortKey="Goetz, David H" sort="Goetz, David H" uniqKey="Goetz D" first="David H." last="Goetz">David H. Goetz</name>
<name sortKey="Hansell, Elizabeth" sort="Hansell, Elizabeth" uniqKey="Hansell E" first="Elizabeth" last="Hansell">Elizabeth Hansell</name>
<name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name>
<name sortKey="Mckerrow, James" sort="Mckerrow, James" uniqKey="Mckerrow J" first="James" last="Mckerrow">James Mckerrow</name>
<name sortKey="Roush, William R" sort="Roush, William R" uniqKey="Roush W" first="William R." last="Roush">William R. Roush</name>
<name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name>
<name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name>
<name sortKey="Zhou, Yanchen" sort="Zhou, Yanchen" uniqKey="Zhou Y" first="Yanchen" last="Zhou">Yanchen Zhou</name>
</country>
</tree>
</affiliations>
</record>

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