title: A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance.
abstract: 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.
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia.|Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Watterson
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: Robinson
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Chappell
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Fry
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Imogen M
authors.initials: IM
authors.lastname: Bermingham
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia.|Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Young
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019556:COS Cells; D002459:Cell Fusion; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000821:virology; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004353:Drug Evaluation, Preclinical; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects* / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D011725:Pyridines / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: C528854:2-(6-((2-(3-hydroxypropyl)-5-methylphenylamino)methyl)-2-(3-morpholin-4-ylpropylamino)benzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol; D001562:Benzimidazoles; D011725:Pyridines; D054852:Small Molecule Libraries