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

Identifieur interne : 000905 ( PascalFrancis/Curation ); précédent : 000904; suivant : 000906

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.
pA  
A01 01  1    @0 0166-3542
A02 01      @0 ARSRDR
A03   1    @0 Antivir. res.
A05       @2 92
A06       @2 2
A08 01  1  ENG  @1 Inhibitors of SARS-CoV entry - Identification using an internally-controlled dual envelope pseudovirion assay
A11 01  1    @1 ZHOU (Yanchen)
A11 02  1    @1 AGUDELO (Juliet)
A11 03  1    @1 LU (Kai)
A11 04  1    @1 GOETZ (David H.)
A11 05  1    @1 HANSELL (Elizabeth)
A11 06  1    @1 CHEN (Yen Ting)
A11 07  1    @1 ROUSH (William R.)
A11 08  1    @1 MCKERROW (James)
A11 09  1    @1 CRAIK (Charles S.)
A11 10  1    @1 AMBERG (Sean M.)
A11 11  1    @1 SIMMONS (Graham)
A14 01      @1 Blood Systems Research Institute, University of California @2 San Francisco, CA 94118 @3 USA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 11 aut.
A14 02      @1 Department of Laboratory Medicine, University of California @2 San Francisco, CA 94143 @3 USA @Z 1 aut. @Z 11 aut.
A14 03      @1 Department of Pharmaceutical Chemistry, University of California @2 San Francisco, CA 94158 @3 USA @Z 4 aut. @Z 9 aut.
A14 04      @1 Department of Pathology and Sandler Center for Drug Discovery, University of California @2 San Francisco, CA 94158 @3 USA @Z 5 aut. @Z 8 aut.
A14 05      @1 Department of Chemistry, Scripps Florida @2 Jupiter, FL 33458 @3 USA @Z 6 aut. @Z 7 aut.
A14 06      @1 SIGA Technologies, Inc @2 Corvallis, OR 97333 @3 USA @Z 10 aut.
A20       @1 187-194
A21       @1 2011
A23 01      @0 ENG
A43 01      @1 INIST @2 18839 @5 354000507853860060
A44       @0 0000 @1 © 2012 INIST-CNRS. All rights reserved.
A45       @0 3/4 p.
A47 01  1    @0 12-0002103
A60       @1 P
A61       @0 A
A64 01  1    @0 Antiviral research
A66 01      @0 GBR
C01 01    ENG  @0 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.
C02 01  X    @0 002B02S05
C03 01  X  FRE  @0 Inhibiteur @5 01
C03 01  X  ENG  @0 Inhibitor @5 01
C03 01  X  SPA  @0 Inhibidor @5 01
C03 02  X  FRE  @0 Virus syndrome respiratoire aigu sévère @2 NW @5 02
C03 02  X  ENG  @0 Severe acute respiratory syndrome virus @2 NW @5 02
C03 02  X  SPA  @0 Severe acute respiratory syndrome virus @2 NW @5 02
C03 03  X  FRE  @0 Identification @5 03
C03 03  X  ENG  @0 Identification @5 03
C03 03  X  SPA  @0 Identificación @5 03
C03 04  X  FRE  @0 Enveloppe @5 04
C03 04  X  ENG  @0 Envelope @5 04
C03 04  X  SPA  @0 Envoltura @5 04
C03 05  X  FRE  @0 Pseudovirion @5 05
C03 05  X  ENG  @0 Pseudovirion @5 05
C03 05  X  SPA  @0 Seudovirión @5 05
C03 06  X  FRE  @0 Antiviral @5 06
C03 06  X  ENG  @0 Antiviral @5 06
C03 06  X  SPA  @0 Antiviral @5 06
C03 07  X  FRE  @0 Criblage haut débit @5 07
C03 07  X  ENG  @0 High throughput screening @5 07
C03 07  X  SPA  @0 Cribado alta productividad @5 07
C03 08  X  FRE  @0 Evaluation performance @5 08
C03 08  X  ENG  @0 Performance evaluation @5 08
C03 08  X  SPA  @0 Evaluación prestación @5 08
C03 09  X  FRE  @0 Technique @5 09
C03 09  X  ENG  @0 Technique @5 09
C03 09  X  SPA  @0 Técnica @5 09
C07 01  X  FRE  @0 Coronavirus @2 NW
C07 01  X  ENG  @0 Coronavirus @2 NW
C07 01  X  SPA  @0 Coronavirus @2 NW
C07 02  X  FRE  @0 Coronaviridae @2 NW
C07 02  X  ENG  @0 Coronaviridae @2 NW
C07 02  X  SPA  @0 Coronaviridae @2 NW
C07 03  X  FRE  @0 Nidovirales @2 NW
C07 03  X  ENG  @0 Nidovirales @2 NW
C07 03  X  SPA  @0 Nidovirales @2 NW
C07 04  X  FRE  @0 Virus @2 NW
C07 04  X  ENG  @0 Virus @2 NW
C07 04  X  SPA  @0 Virus @2 NW
N21       @1 002

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Pascal:12-0002103

Le document en format XML

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<term>Inhibitor</term>
<term>Performance evaluation</term>
<term>Pseudovirion</term>
<term>Severe acute respiratory syndrome virus</term>
<term>Technique</term>
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<term>Inhibiteur</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Identification</term>
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<term>Pseudovirion</term>
<term>Antiviral</term>
<term>Criblage haut débit</term>
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<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>
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