8C8P

Structure of the SARS-CoV-2 spike glycoprotein in complex with the 10D12 heavy-chain-only antibody (local refinement)

8C8P の概要

• エントリーDOI: 10.2210/pdb8c8p/pdb
• EMDBエントリー: 16480 16481 16490
• 分子名称: Heavy-chain-only antibody 10D12, Spike glycoprotein,SARS-CoV-2 spike glycoprotein (2 entities in total)
• 機能のキーワード: complex, spike, glycoprotein, antibody, viral protein
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 183746.30

構造登録者

Serna Martin, I.,Hurdiss, D.L. (登録日: 2023-01-20, 公開日: 2023-02-22, 最終更新日: 2024-11-20)

主引用文献

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

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: 36895554
DOI: 10.3389/fimmu.2023.1111385

実験手法

ELECTRON MICROSCOPY (4.1 Å)