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Structure paper

TitleStructural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 119, Issue 20, Page e2120976119, Year 2022
Publish dateMay 17, 2022
AuthorsJonathan L Torres / Gabriel Ozorowski / Emanuele Andreano / Hejun Liu / Jeffrey Copps / Giulia Piccini / Lorena Donnici / Matteo Conti / Cyril Planchais / Delphine Planas / Noemi Manganaro / Elisa Pantano / Ida Paciello / Piero Pileri / Timothée Bruel / Emanuele Montomoli / Hugo Mouquet / Olivier Schwartz / Claudia Sala / Raffaele De Francesco / Ian A Wilson / Rino Rappuoli / Andrew B Ward /
PubMed AbstractAs the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome ...As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.
External linksProc Natl Acad Sci U S A / PubMed:35549549 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.53 - 6.0 Å
Structure data

24876

7s6i

EMDB-24876, PDB-7s6i:
SARS-CoV-2-6P-Mut2 S protein
Method: EM (single particle) / Resolution: 3.2 Å

24877

7s6j

EMDB-24877, PDB-7s6j:
J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S protein (conformation 1)
Method: EM (single particle) / Resolution: 3.4 Å

24878

7s6k

EMDB-24878, PDB-7s6k:
J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S protein (conformation 2)
Method: EM (single particle) / Resolution: 3.4 Å

24879

7s6l

EMDB-24879, PDB-7s6l:
J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (conformation 3)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-26389: J08 fragment antigen binding in complex with Omicron SARS-CoV-2-6P S protein
Method: EM (single particle) / Resolution: 6.0 Å

PDB-7sbu:
Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a highly potent antibody J08 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.53 Å

Chemicals

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

ChemComp-GOL:
GLYCEROL

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/Immune System / COVID / SARS / CoV-2 / viral glycoprotein / Spike / stabilizing mutations / coronavirus / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / ultrapotent antibody / neutralizing antibody / IMMUNE SYSTEM / SARS-CoV-2 / Antibody / COVID-19 / receptor binding domain

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