Fig. 3: Crystal structure of 76E1 Fab in complex with the SARS-CoV-2 S peptide_809–833.

a, ELISA-based binding activity of 76E1 to 7 conserved peptides within 7 human coronaviruses. Data are presented as mean values of duplicates. b, Overall structure of the 76E1 Fab-peptide complex in ribbon diagram. Heavy and light chains of the 76E1 Fab are shown in light blue and pink, respectively. The SARS-CoV-2 S peptide_809–833 is shown in green. c, Representative simulated annealing composite omit map (contoured at 1.0 σ level) for the peptide. d, Structure of the Fab-peptide interaction interface showing that the peptide assumes an α-helical conformation and is embedded into a cleft formed by the Fab CDR loops H1, H2, H3 and L3. The interacting residues of the peptide are shown in stick model. e, Hydrogen-bonding interactions between the peptide and the Fab. f, Residues Leu822 and Phe823 of the peptide are located in a hydrophobic pocket of the Fab. g, ELISA-based alanine scanning on the S peptide_809–833 of SARS-CoV-2, shown as EC₅₀ values (ng ml⁻¹). h, Sequence alignment of peptide_809–833 (SARS-CoV-2 numbering) among 28 coronaviruses from α, β, γ and δ genera. The epitope residues are shown in red colour. i, ELISA-based binding activity of 76E1 to the S peptides_809–833 of coronavirus from α, β, γ and δ genera, shown as EC₅₀ values. j, Overlay of the crystal structure of the 76E1 Fab-peptide complex (cyan) onto the cryo-EM structure of the SARS-CoV-2 prefusion S trimer (grey) (PDB code 6XR8) based on superposition of the α-helical peptide. The zoomed-in section shows the superposition of the α-helical peptide in the crystal structure of the 76E1 Fab-peptide complex (green) onto the cryo-EM structure of the SARS-CoV-2 S trimer (orange). k, The binding affinity of 76E1 and 76F6 (an RBD antibody isolated in this project) to the prefusion S trimer as determined by BLI. Representative data from 2 independent experiments are shown (a,g,i,k).

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