Fig. 5: Structure and epitope analysis of WRAIR-5001.

a (Left) Crystal structure of WRAIR-5001, in complex with SARS-CoV-2 RBD (white) shown in cartoon representation. Heavy and light chains of WRAIR-5001 are colored dark and light pink, respectively (color scheme applies to all panels in Fig. 5). The ACE2 binding ridge is indicated by Ⓣ. (Right) Structure is shown at 180° rotation. b SARS-CoV-2 RBD shown in surface representation. c Overlay of the SARS-CoV-2 RBD bound ACE2 structure (PDB: 6M0J) onto the WRAIR-5001-RBD complex structure. ACE2 is shown in cartoon representation and colored light blue/grey. d Buried surface area (BSA) for the WRAIR-5001 heavy and light chain CDR loops shown as a bar diagram. e (Left) Key antibody contacting residues of RBD shown as sticks. (Right) Important heavy and light chain contacting residues of contributing CDRs shown as thin sticks and labeled as per antibody coloring scheme. f Structure of WRAIR-5001-RBD complex overlaid onto previously reported antibodies in complex with SARS-CoV-2 RBD (representing frequently observed SARS-CoV-2 epitopes)³⁹. g (Left-Middle) Crystal structures of S309-RBD and WRAIR-2057-RBD complexes overlaid onto the WRAIR-5001-RBD structure. Antibodies S309 and WRAIR-2057 are shown in ribbon representation and colored yellow and red, respectively. (Right) The WRAIR-5001 epitope is colored light and dark pink on the surface of SARS-CoV-2 RBD while S309 and WRAIR-2057 epitopes are outlined and labeled accordingly. h Omicron mutations highlighted as red spheres on the surface of SARS-CoV-2 RBD. The WRAIR-5001 epitope is shown in tubular representation and colored dark pink. i, j Structural superimposition of the WRAIR-5001-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-5001-RBD is overlaid onto the RBD (dark gray surface) from one protomer. Side and top views are shown. k Sequence alignment of WRAIR-5001 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 purple. Symbols *,:, and. denote identical, similar, and less similar residues, respectively. Source data are provided as a Source Data file.