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-Structure paper
タイトル | Structural basis for broad coronavirus neutralization. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 28, Issue 6, Page 478-486, Year 2021 |
掲載日 | 2021年5月12日 |
著者 | Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel Quispe / Benjamin G Hoffstrom / Berend-Jan Bosch / Andrew T McGuire / David Veesler / |
PubMed 要旨 | Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying ...Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine. |
リンク | Nat Struct Mol Biol / PubMed:33981021 |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.4 - 4.7 Å |
構造データ | EMDB-23672: EMDB-23674, PDB-7m5e: PDB-7m51: PDB-7m52: PDB-7m53: PDB-7m55: |
化合物 | ChemComp-GOL: ChemComp-HOH: ChemComp-FOL: ChemComp-NAG: ChemComp-SIA: |
由来 |
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キーワード | ANTIVIRAL PROTEIN / IMMUNE SYSTEM (免疫系) / Broadly neutralizing antibody (中和抗体) / Structural genomics (構造ゲノミクス) / SSGCID / Seattle Structural Genomics Center for Infectious Disease / Center for Structural Genomics of Infectious Diseases / CSGID / VIRAL PROTEIN (ウイルスタンパク質) / MERS-CoV (MERSコロナウイルス) / coronaviruses / antibody (抗体) |