7YC5
Cryo-EM structure of SARS-CoV-2 spike in complex with K202.B bispecific antibody
Summary for 7YC5
| Entry DOI | 10.2210/pdb7yc5/pdb |
| EMDB information | 33734 |
| Descriptor | Spike glycoprotein, Light chain from K202.B, bispecific antibody, Heavy chain from K202.B, bispecific antibody, ... (4 entities in total) |
| Functional Keywords | spike protein, antibody, bispecific antibody, viral protein-immune system complex, viral protein/immune system |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 706901.50 |
| Authors | |
| Primary citation | Kim, J.W.,Heo, K.,Kim, H.J.,Yoo, Y.,Cho, H.S.,Jang, H.J.,Lee, H.Y.,Ko, I.Y.,Woo, J.R.,Cho, Y.B.,Lee, J.H.,Yang, H.R.,Shin, H.G.,Choi, H.L.,Hwang, K.,Kim, S.,Kim, H.,Chun, K.,Lee, S. Novel bispecific human antibody platform specifically targeting a fully open spike conformation potently neutralizes multiple SARS-CoV-2 variants. Antiviral Res., 212:105576-105576, 2023 Cited by PubMed Abstract: Rapid emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted an urgent need for the development of broadly applicable and potently neutralizing antibody platform against the SARS-CoV-2, which can be used for combatting the coronavirus disease 2019 (COVID-19). In this study, based on a noncompeting pair of phage display-derived human monoclonal antibodies (mAbs) specific to the receptor-binding domain (RBD) of SARS-CoV-2 isolated from human synthetic antibody library, we generated K202.B, a novel engineered bispecific antibody with an immunoglobulin G4-single-chain variable fragment design, with sub- or low nanomolar antigen-binding avidity. Compared with the parental mAbs or mAb cocktail, the K202.B antibody showed superior neutralizing potential against a variety of SARS-CoV-2 variants in vitro. Furthermore, structural analysis of bispecific antibody-antigen complexes using cryo-electron microscopy revealed the mode of action of K202.B complexed with a fully open three-RBD-up conformation of SARS-CoV-2 trimeric spike proteins by simultaneously interconnecting two independent epitopes of the SARS-CoV-2 RBD via inter-protomer interactions. Intravenous monotherapy using K202.B exhibited potent neutralizing activity in SARS-CoV-2 wild-type- and B.1.617.2 variant-infected mouse models, without significant toxicity in vivo. The results indicate that this novel approach of development of immunoglobulin G4-based bispecific antibody from an established human recombinant antibody library is likely to be an effective strategy for the rapid development of bispecific antibodies, and timely management against fast-evolving SARS-CoV-2 variants. PubMed: 36870394DOI: 10.1016/j.antiviral.2023.105576 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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