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SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET

Abstract : Targeting the interaction between the SARS-CoV-2 spike protein and human ACE2, its primary cell membrane receptor, is a promising therapeutic strategy to prevent viral entry. Recent in vitro studies revealed that the receptor binding domain (RBD) of the spike protein plays a prominent role in ACE2 binding, yet a simple and quantitative assay for monitoring this interaction in a cellular environment is lacking. Here, we developed an RBD-ACE2 binding assay that is based on time-resolved FRET, which reliably monitors the interaction in a physiologically relevant and cellular context. Because it is modular, the assay can monitor the impact of different cellular components, such as heparan sulfate, lipids, and membrane proteins on the RBD-ACE2 interaction and it can be extended to the full-length spike protein. The assay is HTS compatible and can detect small-molecule competitive and allosteric modulators of the RBD-ACE2 interaction with high relevance for SARS-CoV-2 therapeutics.
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Submitted on : Wednesday, June 1, 2022 - 5:42:00 PM
Last modification on : Friday, June 3, 2022 - 2:17:42 PM

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Erika Cecon, Matilda Burridge, Longxing Cao, Lauren Carter, Rashmi Ravichandran, et al.. SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET. Cell Chemical Biology, Cell Press, 2022, 29 (1), pp.74-83. ⟨10.1016/j.chembiol.2021.06.008⟩. ⟨hal-03685014⟩



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