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-Structure paper
タイトル | The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 2734, Year 2024 |
掲載日 | 2024年3月28日 |
著者 | Daming Zhou / Piyada Supasa / Chang Liu / Aiste Dijokaite-Guraliuc / Helen M E Duyvesteyn / Muneeswaran Selvaraj / Alexander J Mentzer / Raksha Das / Wanwisa Dejnirattisai / Nigel Temperton / Paul Klenerman / Susanna J Dunachie / Elizabeth E Fry / Juthathip Mongkolsapaya / Jingshan Ren / David I Stuart / Gavin R Screaton / |
PubMed 要旨 | Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed ...Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response. |
リンク | Nat Commun / PubMed:38548763 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.2 - 2.7 Å |
構造データ | EMDB-16680, PDB-8cin: EMDB-18807: SD1-2 fab in complex with SARS-COV-2 BA.12.1 Spike Glycoprotein. EMDB-18808, PDB-8r1d: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN (ウイルスタンパク質) / SARS-CoV2 (SARSコロナウイルス2) / spike / glycoprotein (糖タンパク質) / coronavirus (オルトコロナウイルス亜科) / antibody (抗体) / fab / BA.4 / BA.5 / BA.4/5-5 / cross-protective / omicron variant (SARSコロナウイルス2-オミクロン株) / vaccine (ワクチン) / therapeutic (治療) / complex / neutralising / convalescent sera / immune system (免疫系) / SARS-CoV-2 (SARSコロナウイルス2) / SD1 domain / neutralisingm convalescent sera / SD1-2 / BA.2.12.1 / virus (ウイルス) / BA.2.86 / SD1-3 |