A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions.
Magnus Sebastian BauerSophia GruberAdina HauschPriscila da Silva Figueiredo Celestino GomesLukas F MillesThomas NicolausLeonard C SchendelPilar López NavajasErik ProckoDaniel LiethaMarcelo Cardoso Dos Reis MeloRafael C BernardiHermann Eduard GaubJan LipfertPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceIn the dynamic environment of the airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability of the viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic the effect of coughing and sneezing, thereby testing the force stability of SARS-CoV-2 RBD:ACE2 interaction under physiological conditions. Our results reveal a higher force stability of SARS-CoV-2 binding to ACE2 compared to SARS-CoV-1, causing a possible fitness advantage. Our assay is sensitive to blocking agents preventing RBD:ACE2 bond formation. It will thus provide a powerful approach to investigate the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.
Keyphrases
- sars cov
- single molecule
- angiotensin converting enzyme
- angiotensin ii
- respiratory syndrome coronavirus
- living cells
- atomic force microscopy
- high throughput
- body composition
- physical activity
- endothelial cells
- cystic fibrosis
- small molecule
- gene expression
- climate change
- risk assessment
- induced pluripotent stem cells
- binding protein
- pluripotent stem cells