7T67

SARS-CoV-2 S (Spike Glycoprotein) D614G with One(1) RBD Up

7T67 の概要

• エントリーDOI: 10.2210/pdb7t67/pdb
• EMDBエントリー: 25663 25711
• 分子名称: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: virus, coronavirus, sars cov-2, sars-cov-2, spike, d614g, rbd, 1 rbd up, one rbd up, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 392236.35

構造登録者

Byrne, P.O.,McLellan, J.S. (登録日: 2021-12-13, 公開日: 2022-08-24, 最終更新日: 2025-05-28)

主引用文献

Chang, M.R.,Tomasovic, L.,Kuzmina, N.A.,Ronk, A.J.,Byrne, P.O.,Johnson, R.,Storm, N.,Olmedillas, E.,Hou, Y.J.,Schafer, A.,Leist, S.R.,Tse, L.V.,Ke, H.,Coherd, C.,Nguyen, K.,Kamkaew, M.,Honko, A.,Zhu, Q.,Alter, G.,Saphire, E.O.,McLellan, J.S.,Griffiths, A.,Baric, R.S.,Bukreyev, A.,Marasco, W.A.
IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
Nat Commun, 13:5814-5814, 2022

PubMed Abstract: Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.

PubMed: 36192374
DOI: 10.1038/s41467-022-33030-4

実験手法

ELECTRON MICROSCOPY (3 Å)