Fig. 1

Receptor recognition and cell entry mediated by the SARS-CoV-2 spike (S) protein and its inhibition by neutralizing antibodies. a Crystal structure of the receptor-binding domain (RBD) of the original strain of SARS-CoV-2 (extracted from PDB 6M0J). The core region is colored green, and the receptor-binding motif (RBM) is colored orange-red. b Crystal structure of the original strain of SARS-CoV-2 RBD in complex with the human angiotensin-converting enzyme 2 (ACE2) receptor (PDB 6M0J). ACE2 is colored blue. c Cryo-EM structure of the original strain of SARS-CoV-2 S trimer in complex with human ACE2 (PDB 7DF4). The three S subunits are colored green, yellow, and magenta, respectively. d Cryo-EM structure of the SARS-CoV-2 Omicron variant RBD in complex with human ACE2 (PDB 7WPB). The RBM is colored purple. RBM residues that have undergone mutations from the original strain to the Omicron variant are labeled and shown as sticks. e Cryo-EM structure of the SARS-CoV-2 Omicron variant S trimer in complex with human ACE2 (PDB 7WPA). f Mechanisms of neutralization by ACE2-competitive and non-ACE2-competitive RBD-targeting monoclonal antibodies (mAbs). Left, schematic map of the SARS-CoV-2 virion and its binding with the cellular ACE2 receptor through the RBD of the S protein. Middle, CT-P59 (regdanvimab) and LY-CoV555 (bamlanivimab) are representatives of ACE2-competitive mAbs. The composite structural model of the SARS-CoV-2 S trimer/CT-P59 mAb complex was generated by docking the CT-P59 mAb to the S trimer based on the alignment of RBD regions between the crystal structure of the RBD/CT-P59 mAb complex (PDB 7CM4) and the cryo-EM structure of the SARS-CoV-2 S trimer (PDB 6VYB). The illustration of the SARS-CoV-2 S trimer/LY-CoV555 mAb was prepared using PDB 7L3N. Right, S309, LY-CoV1404 (bebtelovimab), and S2X259 are representatives of non-ACE2-competitive mAbs. The composite structural model of the SARS-CoV-2 S trimer/LY-CoV1404 mAb complex was generated by docking the LY-CoV1404 mAb to the S trimer based on the alignment of RBD regions between the crystal structure of the RBD/LY-CoV1404 mAb complex (PDB 7MMO) and the cryo-EM structure of the SARS-CoV-2 S trimer (PDB 6VYB). The illustrations of the SARS-CoV-2 S trimer/S309 mAb and SARS-CoV-2 S trimer/S2X259 mAb were prepared using PDB 6WPS and PDB 7RA8, respectively