A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions
Magnus S. Bauer, Sophia Gruber, Adina Hausch, Priscila da Silva Figueiredo Celestino Gomes, Lukas F. Milles, Thomas Nicolaus, Leonard C. Schendel, Pilar López Navajas, Erik Procko, Daniel Lietha, Marcelo C. R. Melo, Rafael C. Bernardi, Hermann E. Gaub, Jan Lipfert
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.