tetano
Editor, Senior Moderator
Science
. 2022 Jul 12;eabq2679.
doi: 10.1126/science.abq2679. Online ahead of print.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
Jun Siong Low[SUP] #[/SUP][SUP] 1 2 [/SUP], Josipa Jerak[SUP] #[/SUP][SUP] 1 2 [/SUP], M Alejandra Tortorici[SUP] #[/SUP][SUP] 3 [/SUP], Matthew McCallum[SUP] #[/SUP][SUP] 3 [/SUP], Dora Pinto[SUP] #[/SUP][SUP] 4 [/SUP], Antonino Cassotta[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 [/SUP], Federico Mele[SUP] 1 [/SUP], Rana Abdelnabi[SUP] 5 [/SUP], Birgit Weynand[SUP] 6 [/SUP], Julia Noack[SUP] 7 [/SUP], Martin Montiel-Ruiz[SUP] 7 [/SUP], Siro Bianchi[SUP] 4 [/SUP], Fabio Benigni[SUP] 4 [/SUP], Nicole Sprugasci[SUP] 4 [/SUP], Anshu Joshi[SUP] 3 [/SUP], John E Bowen[SUP] 3 [/SUP], Cameron Stewart[SUP] 3 [/SUP], Megi Rexhepaj[SUP] 3 [/SUP], Alexandra C Walls[SUP] 3 8 [/SUP], David Jarrossay[SUP] 1 [/SUP], Diego Morone[SUP] 1 [/SUP], Philipp Paparoditis[SUP] 1 [/SUP], Christian Garzoni[SUP] 9 [/SUP], Paolo Ferrari[SUP] 10 11 12 [/SUP], Alessandro Ceschi[SUP] 10 13 14 15 [/SUP], Johan Neyts[SUP] 5 16 [/SUP], Lisa A Purcell[SUP] 7 [/SUP], Gyorgy Snell[SUP] 7 [/SUP], Davide Corti[SUP] 4 [/SUP], Antonio Lanzavecchia[SUP] #[/SUP][SUP] 4 17 [/SUP], David Veesler[SUP] #[/SUP][SUP] 3 8 [/SUP], Federica Sallusto[SUP] #[/SUP][SUP] 1 2 [/SUP]
Affiliations
Abstract
The coronavirus spike (S) glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus S proteins. This class of 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 beta-coronaviruses, including animal coronavirus 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 show that the fusion peptide-specific mAbs bind with different modalities to a cryptic epitope, which is hidden in prefusion stabilized S, and becomes exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.
. 2022 Jul 12;eabq2679.
doi: 10.1126/science.abq2679. Online ahead of print.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
Jun Siong Low[SUP] #[/SUP][SUP] 1 2 [/SUP], Josipa Jerak[SUP] #[/SUP][SUP] 1 2 [/SUP], M Alejandra Tortorici[SUP] #[/SUP][SUP] 3 [/SUP], Matthew McCallum[SUP] #[/SUP][SUP] 3 [/SUP], Dora Pinto[SUP] #[/SUP][SUP] 4 [/SUP], Antonino Cassotta[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 [/SUP], Federico Mele[SUP] 1 [/SUP], Rana Abdelnabi[SUP] 5 [/SUP], Birgit Weynand[SUP] 6 [/SUP], Julia Noack[SUP] 7 [/SUP], Martin Montiel-Ruiz[SUP] 7 [/SUP], Siro Bianchi[SUP] 4 [/SUP], Fabio Benigni[SUP] 4 [/SUP], Nicole Sprugasci[SUP] 4 [/SUP], Anshu Joshi[SUP] 3 [/SUP], John E Bowen[SUP] 3 [/SUP], Cameron Stewart[SUP] 3 [/SUP], Megi Rexhepaj[SUP] 3 [/SUP], Alexandra C Walls[SUP] 3 8 [/SUP], David Jarrossay[SUP] 1 [/SUP], Diego Morone[SUP] 1 [/SUP], Philipp Paparoditis[SUP] 1 [/SUP], Christian Garzoni[SUP] 9 [/SUP], Paolo Ferrari[SUP] 10 11 12 [/SUP], Alessandro Ceschi[SUP] 10 13 14 15 [/SUP], Johan Neyts[SUP] 5 16 [/SUP], Lisa A Purcell[SUP] 7 [/SUP], Gyorgy Snell[SUP] 7 [/SUP], Davide Corti[SUP] 4 [/SUP], Antonio Lanzavecchia[SUP] #[/SUP][SUP] 4 17 [/SUP], David Veesler[SUP] #[/SUP][SUP] 3 8 [/SUP], Federica Sallusto[SUP] #[/SUP][SUP] 1 2 [/SUP]
Affiliations
- PMID: 35857703
- DOI: 10.1126/science.abq2679
Abstract
The coronavirus spike (S) glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus S proteins. This class of 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 beta-coronaviruses, including animal coronavirus 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 show that the fusion peptide-specific mAbs bind with different modalities to a cryptic epitope, which is hidden in prefusion stabilized S, and becomes exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.