Recreating the biological steps of viral infection on a cell-free bioelectronic platform to profile viral variants of concern

  • Nat Commun. 2024 Jul 3;15(1):5606. doi: 10.1038/s41467-024-49415-6.
Zhongmou Chao  #  1 ,  Ekaterina Selivanovitch  #  1 ,  Konstantinos Kallitsis  2 ,  Zixuan Lu  2 ,  Ambika Pachaury  1 ,  Róisín Owens  2 ,  Susan Daniel  3
Affiliations
  • 1. Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 124 Olin Hall, Ithaca, NY, 14853, USA.
  • 2. Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Dr., Cambridge, CB3 0AS, UK.
  • 3. Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 124 Olin Hall, Ithaca, NY, 14853, USA. [email protected].
  • # Contributed equally.
PMID: 38961055 DOI: 10.1038/s41467-024-49415-6
Abstract

Viral mutations frequently outpace technologies used to detect harmful variants. Given the continual emergence of SARS-CoV-2 variants, platforms that can identify the presence of a virus and its propensity for Infection are needed. Our electronic biomembrane sensing platform recreates distinct SARS-CoV-2 host cell entry pathways and reports the progression of entry as electrical signals. We focus on two necessary entry processes mediated by the viral Spike protein: virus binding and membrane fusion, which can be distinguished electrically. We find that closely related variants of concern exhibit distinct fusion signatures that correlate with trends in cell-based infectivity assays, allowing us to report quantitative differences in their fusion characteristics and hence their infectivity potentials. We use SARS-CoV-2 as our prototype, but we anticipate that this platform can extend to Other enveloped viruses and cell lines to quantifiably assess virus entry.

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