In-Depth Characterization of Zika Virus Inhibitors Using Cell-Based Electrical Impedance

Oeyen, Merel; Meyen, Eef; Doijen, Jordi; Schols, Dominique

doi:10.1128/spectrum.00491-22

Cited by 9 publications

(7 citation statements)

References 56 publications

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“…Of note, the reproducibility of the method is not discussed in the results section, since we want to focus on the individual impedance profiles obtained using the methodology. However, this has been described previously 19 .…”

Section: Representative Resultsmentioning

confidence: 76%

“…Although CEI has not been used to evaluate the course of ZIKV infection or its potential antivirals, its use as a diagnostic tool has been investigated before 18 . In a recent study, the use of the CEI assay to determine the antiviral activity of several ZIKV inhibitors in A549 cells was validated for the first time 19 . This methods article describes this CEI assay in more detail and expands it to various adherent cell lines, as well as a variety of ZIKV strains at various multiplicities of infection (MOI).…”

Section: Introductionmentioning

confidence: 99%

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Cell-Based Electrical Impedance Platform to Evaluate Zika Virus Inhibitors in Real Time

Oeyen

Meyen

Schols

2023

JoVE

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Cell-based electrical impedance (CEI) technology measures changes in impedance caused by a growing or manipulated adherent cell monolayer on culture plate wells embedded with electrodes. The technology can be used to monitor the consequences of Zika virus (ZIKV) infection and adherent cell replication in real time, as this virus is highly cytopathogenic. It is a straightforward assay that does not require the use of labels or invasive methods and has the benefit of providing real-time data. The kinetics of ZIKV infection are highly dependent on the employed cell line, virus strain, and multiplicity of infection (MOI), which cannot be easily studied with conventional endpoint assays. Furthermore, the CEI assay can also be used for the evaluation and characterization of antiviral compounds, which can also have dynamic inhibitory properties over the course of infection. This methods article gives a detailed explanation of the practical execution of the CEI assay and its potential applications in ZIKV research and antiviral research in general.

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Section: Representative Resultsmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Cell-Based Electrical Impedance Platform to Evaluate Zika Virus Inhibitors in Real Time

Oeyen

Meyen

Schols

2023

JoVE

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“… Atienza et al, 2006 , Cerutti et al, 2022 , Chan, 2022 , Cui et al, 2022 , Duan et al, 2022 , Feng et al, 2017 , Giaever and Keese, 1984 , Hoffmann et al, 2020 , Iwata-Yoshikawa et al, 2022 , Jafary et al, 2021 , Kilby et al, 1998 , Koch et al, 2021 , Lan et al, 2022 , Laporte et al, 2021 , Lozada et al, 2021 , Meng et al, 2022 , Montefiori, 2009 , Ngoc Le et al, 2019 , Nguyen et al, 2020 , Oeyen et al, 2022 , Ou et al, 2020 , Pennington and Van de Walle, 2017 , Poumbourios et al, 1999 , Shang et al, 2020 , Stupin et al, 2021 , Suzuki et al, 2022 , Tang et al, 2020 , Vanderheijden et al, 2021 , Vanhulle et al, 2022a , Vanhulle et al, 2022b , Vanhulle et al, 2022c , Walls et al, 2020 , Watterson et al, 2016 , Wrapp et al, 2020 , Xia et al, 2020 , Xu et al, 2016 , Xu et al, 2021 , Zhang et al, 2021 , Zhao et al, 2021 , Zhao et al, 2021 .…”

Section: Uncited Referencesmentioning

confidence: 99%

“…CEI has gained popularity in recent years as a method to monitor dynamic responses of cells. Among other areas of research, CEI has proven effective for cytotoxicity measurements and signalling pathway studies (18,19), and is recently gaining popularity for virological studies as well (20,21). For instance, CEI has been proposed as a generic screening method for fusion inhibitors targeting respiratory syncytial virus (RSV), dengue virus (DENV) and vesicular stomatitis virus (VSV), which are representatives of three viral fusion classes within the enveloped viruses (22).…”

Section: Introductionmentioning

confidence: 99%

Cellular electrical impedance to profile SARS-CoV-2 fusion inhibitors and to assess the fusogenic potential of spike mutants

et al. 2023

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“…CEI has gained popularity in recent years as a method to monitor dynamic responses of cells. Among other areas of research, CEI has proven effective for cytotoxicity measurements and signalling pathway studies (18, 19), and is recently gaining popularity for virological studies as well (20, 21). For instance, CEI has been proposed as a generic screening method for fusion inhibitors targeting respiratory syncytial virus (RSV), dengue virus (DENV) and vesicular stomatitis virus (VSV), which are representatives of three viral fusion classes within the enveloped viruses (22).…”

Section: Introductionmentioning

confidence: 99%

Cellular electrical impedance to profile SARS-CoV-2 fusion inhibitors and to assess the fusogenic potential of spike mutants

Vanhulle

Doijen

Stroobants

et al. 2022

Preprint

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Despite the vaccination campaigns for COVID-19, we still cannot control the spread of SARS-CoV-2, as evidenced by the ongoing circulation of the Omicron variants of concern. This highlights the need for broad-spectrum antivirals to further combat COVID-19 and to be prepared for a new pandemic with a (re-)emerging coronavirus. An interesting target for antiviral drug development is the fusion of the viral envelope with host cell membranes, a crucial early step in the replication cycle of enveloped viruses. In this study, we explored the use of cellular electrical impedance (CEI) to quantitatively monitor morphological changes in real time, resulting from cell-cell fusion elicited by SARS-CoV-2 spike. The impedance signal in CEI-quantified cell-cell fusion correlated with the expression level of SARS-CoV-2 spike in transfected HEK293T cells. For antiviral assessment, we validated the CEI assay with the fusion inhibitor EK1 and measured a concentration-dependent inhibition of SARS-CoV-2 spike mediated cell-cell fusion (IC50 value of 0.13 microM). In addition, CEI was used to confirm the fusion inhibitory activity of the carbohydrate-binding plant lectin UDA against SARS-CoV-2 (IC50 value of 0.55 microM), which complements prior in-house profiling activities. Finally, we explored the utility of CEI in quantifying the fusogenic potential of mutant spike proteins and in comparing the fusion efficiency of SARS-CoV-2 variants of concern. In summary, we demonstrate that CEI is a powerful and sensitive technology that can be applied to studying the fusion process of SARS-CoV-2 and to screening and characterizing fusion inhibitors in a label-free and non-invasive manner.

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In-Depth Characterization of Zika Virus Inhibitors Using Cell-Based Electrical Impedance

Abstract: Zika virus can cause serious disease in humans. Unfortunately, no antiviral drugs are available to treat infection.

Cited by 9 publications

References 56 publications

Cell-Based Electrical Impedance Platform to Evaluate Zika Virus Inhibitors in Real Time

Cell-Based Electrical Impedance Platform to Evaluate Zika Virus Inhibitors in Real Time

Cellular electrical impedance to profile SARS-CoV-2 fusion inhibitors and to assess the fusogenic potential of spike mutants

Cellular electrical impedance to profile SARS-CoV-2 fusion inhibitors and to assess the fusogenic potential of spike mutants

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