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-Structure paper
タイトル | Structures of Omicron spike complexes and implications for neutralizing antibody development. |
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ジャーナル・号・ページ | Cell Rep, Vol. 39, Issue 5, Page 110770, Year 2022 |
掲載日 | 2022年5月3日 |
著者 | Hangtian Guo / Yan Gao / Tinghan Li / Tingting Li / Yuchi Lu / Le Zheng / Yue Liu / Tingting Yang / Feiyang Luo / Shuyi Song / Wei Wang / Xiuna Yang / Henry C Nguyen / Hongkai Zhang / Ailong Huang / Aishun Jin / Haitao Yang / Zihe Rao / Xiaoyun Ji / |
PubMed 要旨 | The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and ...The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies. |
リンク | Cell Rep / PubMed:35477022 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.8 Å |
構造データ | EMDB-32739, PDB-7ws0: EMDB-32740, PDB-7ws1: EMDB-32741, PDB-7ws2: EMDB-32742, PDB-7ws3: EMDB-32743, PDB-7ws4: EMDB-32744, PDB-7ws5: EMDB-32748, PDB-7ws6: EMDB-32749, PDB-7ws7: EMDB-32750, PDB-7ws8: EMDB-32751, PDB-7ws9: EMDB-32752, PDB-7wsa: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / spike glycoprotein / virus / VIRAL PROTEIN / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN/HYDROLASE / VIRAL PROTEIN-HYDROLASE complex |