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Structure paper

TitleLandscape of human antibody recognition of the SARS-CoV-2 receptor binding domain.
Journal, issue, pagesCell Rep, Vol. 37, Issue 2, Page 109822, Year 2021
Publish dateOct 12, 2021
AuthorsAdam K Wheatley / Phillip Pymm / Robyn Esterbauer / Melanie H Dietrich / Wen Shi Lee / Damien Drew / Hannah G Kelly / Li-Jin Chan / Francesca L Mordant / Katrina A Black / Amy Adair / Hyon-Xhi Tan / Jennifer A Juno / Kathleen M Wragg / Thakshila Amarasena / Ester Lopez / Kevin J Selva / Ebene R Haycroft / James P Cooney / Hariprasad Venugopal / Li Lynn Tan / Matthew T O Neill / Cody C Allison / Deborah Cromer / Miles P Davenport / Richard A Bowen / Amy W Chung / Marc Pellegrini / Mark T Liddament / Alisa Glukhova / Kanta Subbarao / Stephen J Kent / Wai-Hong Tham /
PubMed AbstractPotent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike ...Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike. These RBD antibodies ameliorate SARS-CoV-2 infection in mice and hamster models in a dose-dependent manner and in proportion to in vitro, neutralizing potency. Assessing the effect of mutations in the spike protein on antibody recognition and neutralization highlights both potent single antibodies and stereotypic classes of antibodies that are unaffected by currently circulating VOCs, such as B.1.351 and P.1. These neutralizing monoclonal antibodies and others that bind analogous epitopes represent potentially useful future anti-SARS-CoV-2 therapeutics.
External linksCell Rep / PubMed:34610292 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.85 - 8.3 Å
Structure data

EMDB-24642:
SARS-CoV-2 Spike bound to Fab PDI 210
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-24643:
SARS-CoV-2 Spike bound to Fab PDI 96
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-24644:
SARS-CoV-2 Spike bound to Fab PDI 215
Method: EM (single particle) / Resolution: 8.3 Å

EMDB-24645:
SARS-CoV-2 Spike bound to Fab WCSL 119
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-24646:
SARS-CoV-2 Spike bound to Fab WCSL 129
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-24647:
SARS-CoV-2 Spike bound to Fab PDI 93
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-24648:
SARS-CoV-2 Spike bound to Fab PDI 222
Method: EM (single particle) / Resolution: 4.4 Å

24649

7rr0

EMDB-24649, PDB-7rr0:
SARS-CoV-2 receptor binding domain bound to Fab PDI 222
Method: EM (single particle) / Resolution: 3.12 Å

PDB-7mzf:
SARS-CoV-2 receptor binding domain bound to Fab PDI 37
Method: X-RAY DIFFRACTION / Resolution: 2.493 Å

PDB-7mzg:
SARS-CoV-2 receptor binding domain bound to Fab PDI 42
Method: X-RAY DIFFRACTION / Resolution: 2 Å

PDB-7mzh:
SARS-CoV-2 receptor binding domain bound to Fab WCSL 119
Method: X-RAY DIFFRACTION / Resolution: 2.1 Å

PDB-7mzi:
SARS-CoV-2 receptor binding domain bound to Fab WCSL 129
Method: X-RAY DIFFRACTION / Resolution: 1.85 Å

PDB-7mzj:
SARS-CoV-2 receptor binding domain bound to Fab WCSL 129 and Fab PDI 93
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7mzk:
SARS-CoV-2 receptor binding domain bound to Fab WCSL 129 and Fab PDI 96
Method: X-RAY DIFFRACTION / Resolution: 2.25 Å

PDB-7mzl:
SARS-CoV-2 receptor binding domain bound to Fab PDI 210
Method: X-RAY DIFFRACTION / Resolution: 3.7 Å

PDB-7mzm:
SARS-CoV-2 receptor binding domain bound to Fab PDI 215
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

PDB-7mzn:
SARS-CoV-2 receptor binding domain bound to Fab PDI 231
Method: X-RAY DIFFRACTION / Resolution: 3.1 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-CL:
Unknown entry

ChemComp-GOL:
GLYCEROL

ChemComp-HOH:
WATER

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM

ChemComp-CIT:
CITRIC ACID

ChemComp-IPA:
ISOPROPYL ALCOHOL / alkaloid*YM

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / spike / RBD / human antibody / VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / SARS-CoV-2 RBD / Complex / VIRAL PROTEIN-IMMUNE SYSTEM complex

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