Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients.
Journal, issue, pages	Nat Commun, Vol. 14, Issue 1, Page 687, Year 2023
Publish date	Feb 8, 2023
Authors	Romain Rouet / Jake Y Henry / Matt D Johansen / Meghna Sobti / Harikrishnan Balachandran / David B Langley / Gregory J Walker / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / Ohan Mazigi / Peter Schofield / Deborah L Burnett / Simon H J Brown / Marianne Martinello / Bernard Hudson / Nicole Gilroy / Jeffrey J Post / Anthony Kelleher / Hans-Martin Jäck / Christopher C Goodnow / Stuart G Turville / William D Rawlinson / Rowena A Bull / Alastair G Stewart / Philip M Hansbro / Daniel Christ /
PubMed Abstract	Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies ...Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
External links	Nat Commun / PubMed:36755042 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.25 - 3.39 Å
Structure data	25699 7t5o EMDB-25699, PDB-7t5o: VFLIP Spike Trimer with GAR03 Method: EM (single particle) / Resolution: 3.39 Å EMDB-25700: VFLIP Spike Trimer with GAR05 FAB Method: EM (single particle) / Resolution: 3.27 Å PDB-7t72: Epitope-based selection of SARS-CoV-2 neutralizing antibodies from convalescent patients Method: X-RAY DIFFRACTION / Resolution: 3.177 Å PDB-8dxt: Fab arm of antibody GAR12 bound to the receptor binding domain of SARS-CoV-2. Method: X-RAY DIFFRACTION / Resolution: 2.25 Å PDB-8dxu: Fab arms of antibodies GAR03 and 10G4 bound to the receptor binding domain of SARS-CoV-2 in a 1:1:1 complex. Method: X-RAY DIFFRACTION / Resolution: 2.728 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER ChemComp-CL: Unknown entry
Source	severe acute respiratory syndrome-related coronavirus homo sapiens (human) severe acute respiratory syndrome coronavirus 2
Keywords	VIRAL PROTEIN/IMMUNE SYSTEM / spike / Fab / antibody / COVID / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN / SARS-CoV2 / receptor binding domain / neutralizing / ANTIVIRAL PROTEIN / anti-CoV-2 / antibodies / convalescent patients / receptor binding domain.