Key result
Real-time, label-free measurement of cellular electrical impedance can accurately quantify virus-induced cell fusion and determine IC50 values for fusion inhibitors across multiple viral classes.
Cellular electrical impedance provides a generic, high-throughput, reproducible assay for quantifying viral cell-cell fusion and screening fusion inhibitors.
May enable high-throughput antiviral screening; leaves open validation for clinical translation in enveloped viruses.
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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Watterson et al. (2016) studied Virus-induced cell fusion. Cellular electrical impedance (CEI) assay vs. Traditional fusion assays (PRNT, live cell microscopy, luciferase reporter) was evaluated on Quantification of virus-induced cell membrane fusion and IC50 determination of fusion inhibitors. Real-time, label-free measurement of cellular electrical impedance can accurately quantify virus-induced cell fusion and determine IC50 values for fusion inhibitors across multiple viral classes.
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