Q498H and Q498R mutations modify binding of B.1.351 and B.1.617.1/3 variant RBD to HuACE2.

Abstract

(a) Biolayer interferometry was performed with the indicated RBD in solution and HuACE2 immobilise on the sensor. Binding was measured with RBD concentrations of 12, 30, 60, 120nM, and an additional 6nM concentration in some cases. Curves were fitted and used to calculate Kon, Koff and KD. Data are shown as means and SEM for at least three independent experiments. (b) H498 and Y501 in SARS-CoV-2 RBD compete for interaction with Y41 in HuACE2 and the clash between residues is indicated by the overlapping Van der Waals surfaces. The proximity of the H498 side chain is shown with respect to the side chain of a Y501 inserted into our RBD:ACE2 complex structure. (c) R498 and Y501 side chain positions shown along with D38, Y41 and Q42 (PDB accession number 7BH9 [14]).</p