The Q498H mutation enables binding of SARS-CoV-2 RBD to rat ACE2.

Abstract

(a) Kinetic binding constants for RBD binding to RaACE2 measured using biolayer interferometry. Binding was measured with RBD concentrations of 48, 90, 150, 300 and 600nM. Where no binding was detected an additional 1200nM RBD concentration was also tested for binding. RBD with the Q498H mutation binds rat receptor. Data are shown as means and SEM for at least three independent experiments. (b) Rat (RaACE2) and mouse ACE2 (MoACE2) differ from human ACE2 (HuACE2) in key residues contributing to SARS-CoV-2 RBD binding. Residues in human ACE2 at the RBD binding interface are aligned with the corresponding residues in rat and mouse ACE2. Residues that form hydrogen bonds or salt bridges with RBD are in bold and those that differ in rodent are in red. (c) Bonding interactions between Q24 and N487 (d) D30 and K417 (e) Y83 and N487 plus Y489, and (f) K353 and G496, in HuACE2 (yellow) and RBD (green).</p