Fig. 5: H11-H4 and CR3022 have different binding epitopes on RBD and show additive neutralization activities.

a, Superposition using the RBD domains of the H11-H4–RBD complex (colored as in Fig. 4e) with the RBD–ACE2 complex (PDB 6M0J²⁹; ACE2 colored in pale blue). When H11-H4 is bound to RBD, it would prevent ACE2 binding due to steric clashes. b, The region of RBD that engages ACE2 only has a small overlap with the region recognized by H11-H4. The RBD is shown as a molecular surface, regions that only contact ACE2 are highlighted in dark blue, and those that only contact H11-H4 are in red. The two helices and turn of ACE2 that contact RBD are shown in cartoon representation and are colored in light blue. CDR1, CDR2 and CDR3 of H11-H4 are shown in cartoon form and are colored in yellow. Tyr489 and Gln493, which contribute considerably to both binding sites, are highlighted in light green. c, The structure of the ternary complex H11-D4–RBD–CR3022 shows that the nanobody and antibody recognize entirely different epitopes. RBD is colored in red, CR3022 in pale pink and salmon, and H11-D4 in orange. d, Neutralization assay for H11-H4-Fc in the presence of CR3022 at a fixed concentration of 84 nM. The solid gray line represents the control values, with no neutralizing agent. Dashed lines are 50% and 10% of the control, respectively. Data are presented as mean and s.d. of n = 2 technical replicates. The shift in the H11-H4-Fc neutralization curve and the measured ND₅₀ of 2 nM indicate additivity. The experimental plates are shown in Extended Data Fig. 4d.