Fig. 5: P2G3 and P5C3 bind the full-length Omicron spike.

a, Cryo-EM composite density map of the full-length Omicron spike bound to one P5C3 and three P2G3 Fab fragments. Spike protomers are coloured in green, orange and blue, P5C3 Fabs in dark and light orange, P2G3 in black and grey. b, Surface representation of the RBD in the up configuration (green) bound to both P5C3 and P2G3, with heavy and light chains depicted as liquorice ribbons. The buried surface area formed by the Fabs are depicted on the RBD surface and coloured in grey for P2G3 and orange for P5C3. The Omicron mutations are shown in yellow as balls-and-sticks and transparent surfaces. The N-linked glycans at asparagine 331 and 343 are shown as sticks. The right panel shows a 180° rotation of the RBD/P2G3/P5C3 complex relative to the left panel. c, Zoomed-in view of the interacting region of P2G3 with CDR loops of the heavy and light chains specified. Omicron mutations are highlighted in yellow. d, Detailed analysis of the interactions between the Omicron RBD shown as ribbons (green) and the P2G3 Fab heavy and light chains shown as liquorice (black and grey). Residues at the interface are shown as sticks, with potential interactions of interest shown as dashed lines. Omicron mutations are shown as balls-and-sticks in yellow. e, Structures of several class 3 antibodies (Fabs) bound to RBDs were superimposed on the Omicron RBD. The buried surface area formed by the indicated Fabs are outlined on the RBD surface and coloured correspondingly (Fab-RBD structures AZD1061, PDB-7L7E; REGN10987, PDB-6XDG; S309, PDB-7BEP). The Omicron mutations are shown in yellow as balls-and-sticks and transparent surfaces. f, Fab binding angle of attack to the RBD is defined as the line connecting the centroid of the Fab to the centroid of the surface area of the RBD that the Fabs bury. The angle of attack of P2G3 is compared to that of other class 3 antibodies, viewed from multiple angles. RBD is in green, Omicron mutations in yellow. g, P2G3 binding to the full Omicron trimer was modelled by superimposing the Fabs onto the RBD of each protomer. The complex is shown from different sides and top view. P2G3 Fabs are able to bind all RBD-up and RBD-down conformations simultaneously.