Fig. 7: Comparisons of RBD neutralizing Nbs and mAbs.

a Buried surface areas of RBD: Nb and RBD: Fab complexes. VH heavy chain, VL light chain. b Buried surface areas per-interface residue for Nbs and Fabs. c The contact contribution of CDRs and FRs of Nbs and Fabs in RBD binding (using a 6 Å cutoff). Contact contribution % was calculated as # of contacting residues on CDR or FR region/total # of contacting residues. d Quantification of interface cavity. Y-axis is the curvature value. (n = 25 and 60 for Nbs and Fabs, respectively). Box plots indicate median (middle line), 25th, 75th percentile (box), and 5th and 95th percentile (whiskers) as well as outliers (single points). Statistical analysis was performed using a two-tailed student t test, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. e Comparison of contributions from CDRs and FRs for RBD binding between in vivo matured Nbs and in vitro selected Nbs (n = 9 and 15 fpr in vitro selected Nbs and in vivo matured Nbs, respectively). f Representative structures of 7d showing different binding modes (epitope curvature) of an Nb and a Fab. Nbs target concave RBD surfaces to achieve high-affinity binding. g Representative structures of 7e showing the direct involvement of FR2 from an in vitro selected Nb (PDB# 7A29) for RBD interaction.