7SC1

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

Summary for 7SC1

• Entry DOI: 10.2210/pdb7sc1/pdb
• EMDB information: 25008
• Descriptor: Spike glycoprotein, R40-1G8 Fab heavy chain, R40-1G8 Fab light chain, ... (4 entities in total)
• Functional Keywords: immune system, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 9
• Total formula weight: 569034.57

Authors

Fan, C.,Bjorkman, P.J. (deposition date: 2021-09-26, release date: 2022-02-02, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)