학술논문
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Document Type
Article
Author
Low, Jun Siong; Jerak, Josipa; Tortorici, M. Alejandra; McCallum, Matthew; Pinto, Dora; Cassotta, Antonino; Foglierini, Mathilde; Mele, Federico; Abdelnabi, Rana; Weynand, Birgit; Noack, Julia; Montiel-Ruiz, Martin; Bianchi, Siro; Benigni, Fabio; Sprugasci, Nicole; Joshi, Anshu; Bowen, John E.; Stewart, Cameron; Rexhepaj, Megi; Walls, Alexandra C.
Source
Subject
*CORONAVIRUSES
*SARS disease
*IMMUNOGLOBULINS
*GLYCOPROTEINS
*MONOCLONAL antibodies
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Language
ISSN
0036-8075
Abstract
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs. [ABSTRACT FROM AUTHOR]