Proc Natl Acad Sci U S A . Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody

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Proc Natl Acad Sci U S A


. 2022 May 17;119(20):e2120976119.
doi: 10.1073/pnas.2120976119. Epub 2022 May 12.
Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody


Jonathan L Torres[SUP] 1 [/SUP], Gabriel Ozorowski[SUP] 1 [/SUP], Emanuele Andreano[SUP] 2 [/SUP], Hejun Liu[SUP] 1 [/SUP], Jeffrey Copps[SUP] 1 [/SUP], Giulia Piccini[SUP] 3 [/SUP], Lorena Donnici[SUP] 4 [/SUP], Matteo Conti[SUP] 4 [/SUP], Cyril Planchais[SUP] 5 [/SUP], Delphine Planas[SUP] 6 7 [/SUP], Noemi Manganaro[SUP] 2 [/SUP], Elisa Pantano[SUP] 2 [/SUP], Ida Paciello[SUP] 2 [/SUP], Piero Pileri[SUP] 2 [/SUP], Timothée Bruel[SUP] 6 7 [/SUP], Emanuele Montomoli[SUP] 3 8 9 [/SUP], Hugo Mouquet[SUP] 5 [/SUP], Olivier Schwartz[SUP] 6 7 [/SUP], Claudia Sala[SUP] 2 [/SUP], Raffaele De Francesco[SUP] 4 10 [/SUP], Ian A Wilson[SUP] 1 11 [/SUP], Rino Rappuoli[SUP] 2 12 [/SUP], Andrew B Ward[SUP] 1 [/SUP]



Affiliations

• PMID: 35549549
• DOI: 10.1073/pnas.2120976119

Abstract

SignificanceClinical candidate monoclonal antibody J08 binds the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein independent of known escape mutations and is able to potently neutralize most variants of concern (VoCs). Here, we explore these properties using cell-based assays and structural studies. A relatively small epitope footprint high on the receptor binding domain (RBD) ridge and the ability to bind multiple conformational states of the S-protein contribute to strong neutralization across several variants.

Keywords: SARS-CoV-2; cryoelectron microscopy; monoclonal therapy; neutralizing antibody; variants of concern.