Figure 3.
Epitope mapping of SARS-CoV-2 NAbs. (A) SPR kinetics of simultaneous binding of FC05 and three RBD-directed NAbs to SARS-CoV-2 S trimer. (B) SPR-based competitive binding of three RBD-directed NAbs to SARS-CoV-2 S trimer. SARS-CoV-2 S trimer was initially immobilized onto the sensor. One NAb was first injected, followed by the other two, which indicated that these three RBD-directed NAbs competed with each other for binding to the SARS-CoV-2 S trimer. (C) Binding of any one RBD-directed NAb blocks the interactions between ACE2 and SARS-CoV-2 S trimer as assessed by competitive SPR. (D) Structure of SARS-CoV-2 S RBD-FC08-hACE2 complex. The light chain of FC08 Fab is shown in cyan, and the heavy chain in magenta. The RBD and hACE2 are colored in pink and blue, respectively. Residues that constitute the FC08 epitope and the RBM are shown as spheres and colored in green and blue, respectively. The RBM is shown in red. (E) Details of the interactions between the FC08 and SARS-CoV-2 RBD. Some residues involved in the formation of hydrophobic patches (gray mesh) and hydrogen bonds (yellow dash) are shown as sticks and labeled. (F) Cryo-EM structure of SARS-CoV-2 S trimer-FC05 complex. Each S monomer is depicted by various colors and the FC05 Fabs are shown in hot pink (light chains) and purple-blue (heavy chains). (G) Interactions between the NTD and FC05. The loops involved in interactions with FC05 are labeled. (H) Details of the interactions between the FC05 and SARS-CoV-2 NTD. (I) The proposed model of SARS-CoV-2 S trimer in complex with FC05 and FC08. Color scheme is the same as in (D) and (F).
