7SC1

Structure of the SARS-CoV-2 S 6P trimer in complex with the human neutralizing antibody Fab fragment, R40-1G8

7SC1 の概要

• エントリーDOI: 10.2210/pdb7sc1/pdb
• EMDBエントリー: 25008
• 分子名称: Spike glycoprotein, R40-1G8 Fab heavy chain, R40-1G8 Fab light chain, ... (4 entities in total)
• 機能のキーワード: immune system, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 569034.57

構造登録者

Fan, C.,Bjorkman, P.J. (登録日: 2021-09-26, 公開日: 2022-02-02)

主引用文献

Vanshylla, K.,Fan, C.,Wunsch, M.,Poopalasingam, N.,Meijers, M.,Kreer, C.,Kleipass, F.,Ruchnewitz, D.,Ercanoglu, M.S.,Gruell, H.,Munn, F.,Pohl, K.,Janicki, H.,Nolden, T.,Bartl, S.,Stein, S.C.,Augustin, M.,Dewald, F.,Gieselmann, L.,Schommers, P.,Schulz, T.F.,Sander, L.E.,Koch, M.,Luksza, M.,Lassig, M.,Bjorkman, P.J.,Klein, F.
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
Cell Host Microbe, 30:69-82.e10, 2022

PubMed Abstract: A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both "up" and "down" conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.

PubMed: 34973165
DOI: 10.1016/j.chom.2021.12.010

実験手法

ELECTRON MICROSCOPY (3.2 Å)