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-Structure paper
タイトル | Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 7957, Year 2022 |
掲載日 | 2022年12月27日 |
著者 | Mingxi Li / Yifei Ren / Zhen Qin Aw / Bo Chen / Ziqing Yang / Yuqing Lei / Lin Cheng / Qingtai Liang / Junxian Hong / Yiling Yang / Jing Chen / Yi Hao Wong / Jing Wei / Sisi Shan / Senyan Zhang / Jiwan Ge / Ruoke Wang / Jay Zengjun Dong / Yuxing Chen / Xuanling Shi / Qi Zhang / Zheng Zhang / Justin Jang Hann Chu / Xinquan Wang / Linqi Zhang / |
PubMed 要旨 | As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we ...As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines. |
リンク | Nat Commun / PubMed:36575191 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.8 - 3.29 Å |
構造データ | EMDB-33923: Cryo-EM structure of SARS-CoV-2 Omicron spike glycoprotein in complex with three neutralizing nanobody 3-2A2-4 PDB-7x2j: PDB-7x2k: PDB-7x2l: PDB-7x2m: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV / nanobody / spike / receptor binding domain / VIRAL PROTEIN-IMMUNE SYSTEM complex / SARS-CoV-2 |