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Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody
Jonathan 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; Timothee Bruel; Emanuele Montomoli; Hugo Mouquet; Olivier Schwartz; Claudia Sala; Raffaele De Francesco; Ian A. Wilson; Rino Rappuoli; Andrew B. Ward.
Affiliation
  • Jonathan L. Torres; The Scripps Research Institute
  • Gabriel Ozorowski; The Scripps Research Institute
  • Emanuele Andreano; Toscana Life Sciences
  • Hejun Liu; The Scripps Research Institute
  • Jeffrey Copps; The Scripps Research Institute
  • Giulia Piccini; Istituto Nazionale Genetica Molecolare
  • Lorena Donnici; Istituto Nazionale Genetica Molecolare
  • Matteo Conti; Istituto Nazionale Genetica Molecolare
  • Cyril Planchais; Institut Pasteur
  • Delphine Planas; Institut Pasteur
  • Noemi Manganaro; Toscana Life Sciences
  • Elisa Pantano; Toscana Life Sciences
  • Ida Paciello; Toscana Life Sciences
  • Piero Pileri; Toscana Life Sciences
  • Timothee Bruel; Institut Pasteur
  • Emanuele Montomoli; VisMederi S.r.l
  • Hugo Mouquet; Institut Pasteur
  • Olivier Schwartz; Institut Pasteur
  • Claudia Sala; Toscana Life Sciences
  • Raffaele De Francesco; Istituto Nazionale Genetica Molecolare
  • Ian A. Wilson; The Scripps Research Institute
  • Rino Rappuoli; Toscana Life Sciences
  • Andrew B. Ward; The Scripps Research Institute
Preprint in English | bioRxiv | ID: ppbiorxiv-462234
ABSTRACT
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 a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy. One Sentence SummaryPotent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.
License
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint
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