7KLG

SARS-CoV-2 RBD in complex with Fab 15033

7KLG の概要

• エントリーDOI: 10.2210/pdb7klg/pdb
• 分子名称: Fab 15033 heavy chain, Fab 15033 light chain, Spike glycoprotein, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, spike glycoprotein, fab, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 139627.82

構造登録者

Li, Z.,Rini, J.M. (登録日: 2020-10-30, 公開日: 2021-02-10, 最終更新日: 2024-11-20)

主引用文献

Miersch, S.,Li, Z.,Saberianfar, R.,Ustav, M.,Brett Case, J.,Blazer, L.,Chen, C.,Ye, W.,Pavlenco, A.,Gorelik, M.,Garcia Perez, J.,Subramania, S.,Singh, S.,Ploder, L.,Ganaie, S.,Chen, R.E.,Leung, D.W.,Pandolfi, P.P.,Novelli, G.,Matusali, G.,Colavita, F.,Capobianchi, M.R.,Jain, S.,Gupta, J.B.,Amarasinghe, G.K.,Diamond, M.S.,Rini, J.,Sidhu, S.S.
Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations.
J.Mol.Biol., 433:167177-167177, 2021

PubMed Abstract: Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and tetravalent versions block entry with a potency exceeding bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show increased tolerance to potential virus escape mutants and an emerging variant of concern. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, and our strategy can be applied to virtually any antibody drug.

PubMed: 34329642
DOI: 10.1016/j.jmb.2021.167177

実験手法

X-RAY DIFFRACTION (3.2 Å)