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-Structure paper
タイトル | Broad betacoronavirus neutralization by a stem helix-specific human antibody. |
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ジャーナル・号・ページ | Science, Vol. 373, Issue 6559, Page 1109-1116, Year 2021 |
掲載日 | 2021年9月3日 |
著者 | Dora Pinto / Maximilian M Sauer / Nadine Czudnochowski / Jun Siong Low / M Alejandra Tortorici / Michael P Housley / Julia Noack / Alexandra C Walls / John E Bowen / Barbara Guarino / Laura E Rosen / Julia di Iulio / Josipa Jerak / Hannah Kaiser / Saiful Islam / Stefano Jaconi / Nicole Sprugasci / Katja Culap / Rana Abdelnabi / Caroline Foo / Lotte Coelmont / Istvan Bartha / Siro Bianchi / Chiara Silacci-Fregni / Jessica Bassi / Roberta Marzi / Eneida Vetti / Antonino Cassotta / Alessandro Ceschi / Paolo Ferrari / Pietro E Cippà / Olivier Giannini / Samuele Ceruti / Christian Garzoni / Agostino Riva / Fabio Benigni / Elisabetta Cameroni / Luca Piccoli / Matteo S Pizzuto / Megan Smithey / David Hong / Amalio Telenti / Florian A Lempp / Johan Neyts / Colin Havenar-Daughton / Antonio Lanzavecchia / Federica Sallusto / Gyorgy Snell / Herbert W Virgin / Martina Beltramello / Davide Corti / David Veesler / |
PubMed 要旨 | The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We ...The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection. |
リンク | Science / PubMed:34344823 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.67 - 4.2 Å |
構造データ | EMDB-24533: PDB-7rnj: |
化合物 | ChemComp-SO4: ChemComp-HOH: |
由来 |
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キーワード | ANTIVIRAL PROTEIN / IMMUNE SYSTEM / COVID-19 / SARS-CoV-2 / neutralizing monoclonal antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |