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	Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.
Journal, issue, pages	bioRxiv, Year 2021
Publish date	Dec 24, 2021
Authors	Lei Peng / Yingxia Hu / Madeleine C Mankowski / Ping Ren / Rita E Chen / Jin Wei / Min Zhao / Tongqing Li / Therese Tripler / Lupeng Ye / Ryan D Chow / Zhenhao Fang / Chunxiang Wu / Matthew B Dong / Matthew Cook / Guilin Wang / Paul Clark / Bryce Nelson / Daryl Klein / Richard Sutton / Michael S Diamond / Craig B Wilen / Yong Xiong / Sidi Chen /
PubMed Abstract	COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging ...COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.
External links	bioRxiv / PubMed:34981065 / PubMed Central
Methods	EM (single particle)
Resolution	2.97 - 3.42 Å
Structure data	24060 7mw2 EMDB-24060, PDB-7mw2: Structure of the SARS-CoV-2 Spike trimer with all RBDs down in complex with the Fab fragment of human neutralizing antibody clone 6 Method: EM (single particle) / Resolution: 2.97 Å 24061 7mw3 EMDB-24061, PDB-7mw3: Structure of the SARS-CoV-2 Spike trimer with two RBDs down in complex with the Fab fragment of human neutralizing antibody clone 6 Method: EM (single particle) / Resolution: 3.15 Å 24062 7mw4 EMDB-24062, PDB-7mw4: Structure of the SARS-CoV-2 Spike trimer with one RBD down in complex with the Fab fragment of human neutralizing antibody clone 6 Method: EM (single particle) / Resolution: 3.42 Å 24063 7mw5 EMDB-24063, PDB-7mw5: Structure of the SARS-CoV-2 Spike trimer with one RBD down in complex with the Fab fragment of human neutralizing antibody clone 2 Method: EM (single particle) / Resolution: 3.42 Å 24064 7mw6 EMDB-24064, PDB-7mw6: Structure of the SARS-CoV-2 Spike trimer with three RBDs up in complex with the Fab fragment of human neutralizing antibody clone 2 Method: EM (single particle) / Resolution: 3.22 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 / viral protein / antibody / VIRAL PROTEIN-Immune System complex