Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Low JS, Jerak J, Tortorici MA, McCallum M, Pinto D, Cassotta A, Foglierini M, Mele F, Abdelnabi R, Weynand B, Noack J, Montiel-Ruiz M, Bianchi S, Benigni F, Sprugasci N, Joshi A, Bowen JE, Walls AC, Jarrossay D, Morone D, Paparoditis P, Garzoni C, Ferrari P, Ceschi A, Neyts J, Purcell LA, Snell G, Corti D, Lanzavecchia A, Veesler D, Sallusto F

Coronaviruses use diverse Spike (S) glycoproteins to attach to host receptors and fuse with target cells. Using a broad screening approach, we isolated from SARS-CoV-2 immune donors seven monoclonal antibodies (mAbs) that bind to all human alpha and beta coronavirus S proteins. These mAbs recognize the fusion peptide and acquire ...

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high affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha and beta coronaviruses, including Omicron BA.1 variant and bat WIV-1, and reduce viral titers and pathology in vivo. Structural and functional analyses show that the fusion peptide-specific mAbs bind with different modalities to a cryptic epitope which is concealed by prefusion-stabilizing 2P mutations and becomes exposed upon binding of ACE2 or ACE2-mimicking mAbs. This study identifies a new class of pan-coronavirus neutralizing mAbs and reveals a receptor-induced conformational change in the S protein that exposes the fusion peptide region.

Date: Mar. 30, 2022

Status: Preliminary Report

View Source: doi: 10.1101/2022.03.30.486377

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