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| Title | A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification. |
|---|---|
| Journal, issue, pages | Cell, Vol. 187, Issue 25, Page 7196-7213.e26, Year 2024 |
| Publish date | Dec 12, 2024 |
Authors | Laura E Rosen / M Alejandra Tortorici / Anna De Marco / Dora Pinto / William B Foreman / Ashley L Taylor / Young-Jun Park / Dana Bohan / Tyson Rietz / John M Errico / Kevin Hauser / Ha V Dang / Justin W Chartron / Martina Giurdanella / Giuseppe Cusumano / Christian Saliba / Fabrizia Zatta / Kaitlin R Sprouse / Amin Addetia / Samantha K Zepeda / Jack Brown / Jimin Lee / Exequiel Dellota / Anushka Rajesh / Julia Noack / Qiqing Tao / Yvonne DaCosta / Brian Tsu / Rima Acosta / Sambhavi Subramanian / Guilherme Dias de Melo / Lauriane Kergoat / Ivy Zhang / Zhuoming Liu / Barbara Guarino / Michael A Schmid / Gretja Schnell / Jessica L Miller / Florian A Lempp / Nadine Czudnochowski / Elisabetta Cameroni / Sean P J Whelan / Hervé Bourhy / Lisa A Purcell / Fabio Benigni / Julia di Iulio / Matteo Samuele Pizzuto / Antonio Lanzavecchia / Amalio Telenti / Gyorgy Snell / Davide Corti / David Veesler / Tyler N Starr / ![]() |
| PubMed Abstract | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine. |
External links | Cell / PubMed:39383863 / PubMed Central |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 1.67 - 3.3 Å |
| Structure data | EMDB-43813, PDB-9asd: EMDB-43842, PDB-9au2: ![]() PDB-8s6m: ![]() PDB-9atm: ![]() PDB-9au1: |
| Chemicals | ![]() ChemComp-EDO: ![]() ChemComp-NAG: ![]() ChemComp-NI: ![]() ChemComp-TRS: ![]() ChemComp-HOH: ![]() ChemComp-CL: ![]() ChemComp-K: ![]() ChemComp-ACY: ![]() ChemComp-EPE: |
| Source |
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Keywords | VIRAL PROTEIN / Sarbecoviruses / Spike glycoprotein / fusion protein / neutralizing antibodies / inhibitor / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / Structural Genomics Consortium / SGC |
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Sarbecovirus
homo sapiens (human)
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