Fig. 4: Structure and epitope analysis of WRAIR-5021.

a (Left) Crystal structure of WRAIR-5021, in complex with SARS-CoV-2 RBD (white) shown in cartoon representation. WRAIR-5021 heavy and light chains are colored dark and light green, respectively (color scheme applies to all panels in Fig. 4). The ACE2 binding ridge is indicated by Ⓣ. (Right) Structure is shown at 90° rotation. b (Left) Overlay of SARS-CoV-2 RBD bound ACE2 structure (PDB: 6M0J) onto the WRAIR-5021-RBD complex structure. ACE2 is shown in light blue/grey surface. (Right) Epitope of WRAIR-5021 shown on the surface of the RBD. The ACE2 epitope is outlined in cyan. c Buried surface area (BSA) for the CDR loops is shown as a bar diagram. d (Left) Key antibody contacting residues of RBD are shown as sticks, with residues reported in VoCs in red. (Right) Important heavy and light chain contacting residues shown as thin sticks. RBD residues reported in VoCs are represented in red sticks. e Structure of the WRAIR-5001-RBD complex overlaid onto previously reported antibodies in complex with SARS-CoV-2 RBD (representing frequently observed SARS-CoV-2 epitopes³⁹). f (Left) Omicron mutations highlighted as red spheres on the surface of SARS-CoV-2 RBD. The WRAIR-5021 epitope is shown in tubular representation and colored dark green. Omicron mutations that fall within the mAb epitope are shown as green spheres and labeled. (Right) RBD sequence alignment with WRAIR-5021 epitope indicated. Mutated residues in VoCs are highlighted in red. BSA for epitope residues are shown in the bar graph at the bottom. g Structural superimposition of the WRAIR-5021-RBD complex with closed (all RBD down conformation, PDB code: 6ZGE) and open (1-RBD-up, PDB: 6X2B) conformations of SARS-CoV-2 S-2P. WRAIR-5021-RBD is overlaid onto the RBD (dark gray surface) from one protomer. Side and top views are shown. h Sequence alignment of WRAIR-5021 with its precursor germline gene. CDRs are shaded grey, with residue numbering and CDR loops designated using the Kabat system. Residues interacting with the RBD are colored green. Symbols *,:, and. denote identical, similar, and less similar residues, respectively. Source data are provided as a Source Data file.