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



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.