8C8P
Structure of the SARS-CoV-2 spike glycoprotein in complex with the 10D12 heavy-chain-only antibody (local refinement)
Summary for 8C8P
| Entry DOI | 10.2210/pdb8c8p/pdb |
| EMDB information | 16480 16481 16490 |
| Descriptor | Heavy-chain-only antibody 10D12, Spike glycoprotein,SARS-CoV-2 spike glycoprotein (2 entities in total) |
| Functional Keywords | complex, spike, glycoprotein, antibody, viral protein |
| Biological source | Mus musculus More |
| Total number of polymer chains | 2 |
| Total formula weight | 183746.30 |
| Authors | Serna Martin, I.,Hurdiss, D.L. (deposition date: 2023-01-20, release date: 2023-02-22, Last modification date: 2024-11-20) |
| Primary citation | Du, W.,Janssens, R.,Mykytyn, A.Z.,Li, W.,Drabek, D.,van Haperen, R.,Chatziandreou, M.,Rissmann, M.,van der Lee, J.,van Dortmondt, M.,Martin, I.S.,van Kuppeveld, F.J.M.,Hurdiss, D.L.,Haagmans, B.L.,Grosveld, F.,Bosch, B.J. Avidity engineering of human heavy-chain-only antibodies mitigates neutralization resistance of SARS-CoV-2 variants. Front Immunol, 14:1111385-1111385, 2023 Cited by PubMed Abstract: Emerging SARS-CoV-2 variants have accrued mutations within the spike protein rendering most therapeutic monoclonal antibodies against COVID-19 ineffective. Hence there is an unmet need for broad-spectrum mAb treatments for COVID-19 that are more resistant to antigenically drifted SARS-CoV-2 variants. Here we describe the design of a biparatopic heavy-chain-only antibody consisting of six antigen binding sites recognizing two distinct epitopes in the spike protein NTD and RBD. The hexavalent antibody showed potent neutralizing activity against SARS-CoV-2 and variants of concern, including the Omicron sub-lineages BA.1, BA.2, BA.4 and BA.5, whereas the parental components had lost Omicron neutralization potency. We demonstrate that the tethered design mitigates the substantial decrease in spike trimer affinity seen for escape mutations for the hexamer components. The hexavalent antibody protected against SARS-CoV-2 infection in a hamster model. This work provides a framework for designing therapeutic antibodies to overcome antibody neutralization escape of emerging SARS-CoV-2 variants. PubMed: 36895554DOI: 10.3389/fimmu.2023.1111385 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.1 Å) |
Structure validation
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