A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions.

Bauer, Magnus S; Gruber, Sophia; Hausch, Adina; Gomes, Priscila S F C; Milles, Lukas F; Nicolaus, Thomas; Schendel, Leonard C; Navajas, Pilar López et al. · Proc Natl Acad Sci U S A · 2022

basic_science · Level V

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Abstract

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.

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