Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody - Institut Pasteur Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2022

Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody

Giulia Piccini
Noemi Manganaro
Piero Pileri
Hugo Mouquet

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 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.
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pasteur-04082754 , version 1 (26-04-2023)

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Jonathan Torres, Gabriel Ozorowski, Emanuele Andreano, Hejun Liu, Jeffrey Copps, et al.. Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (20), pp.e2120976119. ⟨10.1073/pnas.2120976119⟩. ⟨pasteur-04082754⟩
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