National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
Intramural
United States
Citation
Journal: Science / Year: 2021 Title: Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Authors: Lingshu Wang / Tongqing Zhou / Yi Zhang / Eun Sung Yang / Chaim A Schramm / Wei Shi / Amarendra Pegu / Olamide K Oloniniyi / Amy R Henry / Samuel Darko / Sandeep R Narpala / Christian ...Authors: Lingshu Wang / Tongqing Zhou / Yi Zhang / Eun Sung Yang / Chaim A Schramm / Wei Shi / Amarendra Pegu / Olamide K Oloniniyi / Amy R Henry / Samuel Darko / Sandeep R Narpala / Christian Hatcher / David R Martinez / Yaroslav Tsybovsky / Emily Phung / Olubukola M Abiona / Avan Antia / Evan M Cale / Lauren A Chang / Misook Choe / Kizzmekia S Corbett / Rachel L Davis / Anthony T DiPiazza / Ingelise J Gordon / Sabrina Helmold Hait / Tandile Hermanus / Prudence Kgagudi / Farida Laboune / Kwanyee Leung / Tracy Liu / Rosemarie D Mason / Alexandra F Nazzari / Laura Novik / Sarah O'Connell / Sijy O'Dell / Adam S Olia / Stephen D Schmidt / Tyler Stephens / Christopher D Stringham / Chloe Adrienna Talana / I-Ting Teng / Danielle A Wagner / Alicia T Widge / Baoshan Zhang / Mario Roederer / Julie E Ledgerwood / Tracy J Ruckwardt / Martin R Gaudinski / Penny L Moore / Nicole A Doria-Rose / Ralph S Baric / Barney S Graham / Adrian B McDermott / Daniel C Douek / Peter D Kwong / John R Mascola / Nancy J Sullivan / John Misasi / Abstract: The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. ...The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC) 0.3 to 11.1 nanograms per milliliter; IC 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
History
Deposition
Apr 29, 2021
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Header (metadata) release
Jul 28, 2021
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Map release
Jul 28, 2021
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Update
Aug 25, 2021
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Current status
Aug 25, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Entire : SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1
Entire
Name: SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1
Components
Complex: SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1
Protein or peptide: B1-182.1 Fab heavy chain
Protein or peptide: B1-182.1 Fab light chain
Protein or peptide: Spike glycoprotein
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
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Supramolecule #1: SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1
Supramolecule
Name: SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: Complex prepared by mixing SARS-CoV-2 spike protein and Fab fragment of antibody at a molar ratio of 1:3.6.
Source (natural)
Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weight
Theoretical: 539.951 KDa
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Macromolecule #1: B1-182.1 Fab heavy chain
Macromolecule
Name: B1-182.1 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 4 seconds before plugging..
Details
Complex at 0.5 mg/mL concentration in the presence of 0.005% DDM
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: OTHER / Average electron dose: 40.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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