Neutralization of SARS-CoV-2 by IgM-14 via engagement of two distinct spike epitopes
Fig 5
Analysis of the secondary binding site.
A, Structural analysis of the secondary binding site. B, MM/PBSA analysis of changes in RBD/Fab-14 complex binding free energy changes caused by indicated mutations. C-D, Neutralization curves of IgG-14 (C) or IgM-14 (D) against mNG SARS-CoV-2 D614G (reference) and mNG SARS-CoV-2 D614G+N331Q + L335A (N331Q+L335A). E-F, Neutralization curves of IgG-14 (E) or IgM-14 (F) against mNG SARS-CoV-2 D614G+E484K (E484K) and mNG SARS-CoV-2 D614G+E484K + N331Q+L335A (E484K+N331Q + L335A). Means and standard deviation from three independent experiments are shown in panels C-F. G, Summary of EC50 values of IgG-14 or IgM-14 against indicated SARS-CoV-2 mutants. H, A model of IgM-14 complexed with SARS-CoV-2 spike trimer shows different modes of spike-IgM-14 interactions. The coordinates of IgM were taken from a published report41 by Chen, Q. et al. and adjusted by rigid body movement of the Fab arms while preserving the integrity of the Fab tethers.