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. 2020 Sep 16;183(4):1024–1042.e21. doi: 10.1016/j.cell.2020.09.037

Figure 5.

Figure 5

The S2A4 mAb Promotes SARS-CoV-2 S Opening through Binding to a Cryptic Epitope

(A) SARS-CoV-2 S pseudovirus neutralization assay indicating an IC50 of 3.5 μg/mL.

(B and C) Molecular surface representation of the SARS-CoV-2 S/S2A4 Fab complex cryo-EM structure with three RBDs open viewed along two orthogonal orientations. Each SARS-CoV-2 protomer is colored distinctly (cyan, pink, and gold), and N-linked glycans are rendered as dark blue surfaces. The S2A4 light and heavy chains are colored magenta and purple, respectively.

(D and E) Zoomed-in views of the contacts formed between S2A4 and the RBD with selected side chains shown.

(F) S2A4 and ACE2 (dark green) bind distinct RBD epitopes but would clash via steric hindrance. The red star indicates steric clashes.

(G) BLI binding competition between S2A4 and ACE2 for binding to the SARS-CoV-2 RBD.

(H) Molecular surface representation of the SARS-CoV-2 RBD (gray) with the S2A4 epitope colored by amino acid residue conservation with SARS-CoV. The position of the SARS-CoV N357 glycan is indicated with red dotted lines.