Detection of SARS-CoV-2 spike protein binding to ACE2 in living cells by TR-FRET

STAR Protoc. 2022 Mar 18;3(1):101024. doi: 10.1016/j.xpro.2021.101024. Epub 2021 Nov 22.

Abstract

The SARS-CoV-2 coronavirus infects human cells through the interaction of the viral envelope spike protein (IPR044366) with the human angiotensin-converting enzyme 2 (ACE2), expressed at the surface of target cells. Here, we describe a detailed protocol to measure the binding of the receptor binding domain (RBD) of spike to ACE2 by time-resolved fluorescence resonance energy transfer (TR-FRET). The assay detects the spike/ACE2 interaction in physiologically relevant cellular contexts and is suitable for high-throughput investigation of interfering small-molecule compounds and antibodies. For complete details on the use and execution of this protocol, please refer to Cecon et al. (2021).

Keywords: Cell Biology; Cell culture; Cell-based Assays; High Throughput Screening; Molecular Biology; Molecular/Chemical Probes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • Fluorescence Resonance Energy Transfer / methods*
  • HEK293 Cells
  • Humans
  • Protein Binding / physiology
  • SARS-CoV-2 / metabolism*
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2