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A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance

Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, rep...

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Autores principales: Watterson, Daniel, Robinson, Jodie, Chappell, Keith J., Butler, Mark S., Edwards, David J., Fry, Scott R., Bermingham, Imogen M., Cooper, Matthew A., Young, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792136/
https://www.ncbi.nlm.nih.gov/pubmed/26976324
http://dx.doi.org/10.1038/srep22791
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author Watterson, Daniel
Robinson, Jodie
Chappell, Keith J.
Butler, Mark S.
Edwards, David J.
Fry, Scott R.
Bermingham, Imogen M.
Cooper, Matthew A.
Young, Paul R.
author_facet Watterson, Daniel
Robinson, Jodie
Chappell, Keith J.
Butler, Mark S.
Edwards, David J.
Fry, Scott R.
Bermingham, Imogen M.
Cooper, Matthew A.
Young, Paul R.
author_sort Watterson, Daniel
collection PubMed
description Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus.
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spelling pubmed-47921362016-03-16 A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance Watterson, Daniel Robinson, Jodie Chappell, Keith J. Butler, Mark S. Edwards, David J. Fry, Scott R. Bermingham, Imogen M. Cooper, Matthew A. Young, Paul R. Sci Rep Article Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. Nature Publishing Group 2016-03-15 /pmc/articles/PMC4792136/ /pubmed/26976324 http://dx.doi.org/10.1038/srep22791 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Watterson, Daniel
Robinson, Jodie
Chappell, Keith J.
Butler, Mark S.
Edwards, David J.
Fry, Scott R.
Bermingham, Imogen M.
Cooper, Matthew A.
Young, Paul R.
A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title_full A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title_fullStr A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title_full_unstemmed A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title_short A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
title_sort generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792136/
https://www.ncbi.nlm.nih.gov/pubmed/26976324
http://dx.doi.org/10.1038/srep22791
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