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-Structure paper
タイトル | The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 119, Issue 34, Page e2204256119, Year 2022 |
掲載日 | 2022年8月23日 |
著者 | Hualong Xiong / Hui Sun / Siling Wang / Lunzhi Yuan / Liqin Liu / Yuhe Zhu / Jinlei Zhang / Yang Huang / Ruoyao Qi / Yao Jiang / Jian Ma / Ming Zhou / Yue Ma / Rao Fu / Siping Yan / Mingxi Yue / Yangtao Wu / Min Wei / Yizhen Wang / Tingting Li / Yingbin Wang / Zizheng Zheng / Hai Yu / Tong Cheng / Shaowei Li / Quan Yuan / Jun Zhang / Yi Guan / Qingbing Zheng / Tianying Zhang / Ningshao Xia / |
PubMed 要旨 | Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing ...Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants. |
リンク | Proc Natl Acad Sci U S A / PubMed:35972965 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.48 - 6.56 Å |
構造データ | EMDB-33047, PDB-7x7t: EMDB-33048, PDB-7x7u: EMDB-33049, PDB-7x7v: EMDB-33050: Cryo-EM structure of SARS-CoV-2 Delta variant spike protein in complex with three nAbs X01, X10 and X17 EMDB-33051: Cryo-EM structure of SARS-CoV spike protein in complex with three nAbs X01, X10 and X17 EMDB-33052: Cryo-EM structure of SARS-CoV-2 Omicron variant spike protein in complex with three nAbs X01, X10 and X17 |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Neutralizing antibody / Cryo-EM / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / SARS-CoV-2 Delta variant |