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	Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations.
Journal, issue, pages	J Mol Biol, Vol. 433, Issue 19, Page 167177, Year 2021
Publish date	Sep 17, 2021
Authors	Shane Miersch / Zhijie Li / Reza Saberianfar / Mart Ustav / James Brett Case / Levi Blazer / Chao Chen / Wei Ye / Alevtina Pavlenco / Maryna Gorelik / Julia Garcia Perez / Suryasree Subramania / Serena Singh / Lynda Ploder / Safder Ganaie / Rita E Chen / Daisy W Leung / Pier Paolo Pandolfi / Giuseppe Novelli / Giulia Matusali / Francesca Colavita / Maria R Capobianchi / Suresh Jain / J B Gupta / Gaya K Amarasinghe / Michael S Diamond / James Rini / Sachdev S Sidhu /
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 ...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.
External links	J Mol Biol / PubMed:34329642 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	3 - 6.4 Å
Structure data	22925 7kmk EMDB-22925, PDB-7kmk: cryo-EM structure of SARS-CoV-2 spike in complex with Fab 15033-7, two RBDs bound Method: EM (single particle) / Resolution: 4.2 Å 22926 7kml EMDB-22926, PDB-7kml: cryo-EM structure of SARS-CoV-2 spike in complex with Fab 15033-7, three RBDs bound Method: EM (single particle) / Resolution: 3.8 Å 23064 7kxj EMDB-23064, PDB-7kxj: SARS-CoV-2 spike protein in complex with Fab 15033-7, 3-"up", asymmetric Method: EM (single particle) / Resolution: 6.4 Å 23065 7kxk EMDB-23065, PDB-7kxk: SARS-CoV-2 spike protein in complex with Fab 15033-7, 2-"up"-1-"down" conformation Method: EM (single particle) / Resolution: 5.0 Å PDB-7klg: SARS-CoV-2 RBD in complex with Fab 15033 Method: X-RAY DIFFRACTION / Resolution: 3.2 Å PDB-7klh: SARS-CoV-2 RBD in complex with Fab 15033-7 Method: X-RAY DIFFRACTION / Resolution: 3.0 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine
Source	severe acute respiratory syndrome coronavirus 2 homo sapiens (human)
Keywords	VIRAL PROTEIN/Immune System / SARS-CoV-2 / spike glycoprotein / Fab / VIRAL PROTEIN-Immune System complex / spike / VIRAL PROTEIN