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-Structure paper
タイトル | Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes. |
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ジャーナル・号・ページ | bioRxiv, Year 2021 |
掲載日 | 2021年3月10日 |
著者 | Dapeng Sun / Zhe Sang / Yong Joon Kim / Yufei Xiang / Tomer Cohen / Anna K Belford / Alexis Huet / James F Conway / Ji Sun / Derek J Taylor / Dina Schneidman-Duhovny / Cheng Zhang / Wei Huang / Yi Shi / |
PubMed 要旨 | There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel ...There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel aerosolization route to treat SARS-CoV-2 infections efficiently. However, it remains unknown if they possess broadly neutralizing activities against the prevalent circulating strains. We found that potent neutralizing Nbs are highly resistant to the convergent variants of concern that evade a large panel of neutralizing antibodies (Abs) and significantly reduce the activities of convalescent or vaccine-elicited sera. Subsequent determination of 9 high-resolution structures involving 6 potent neutralizing Nbs by cryoelectron microscopy reveals conserved and novel epitopes on virus spike inaccessible to Abs. Systematic structural comparison of neutralizing Abs and Nbs provides critical insights into how Nbs uniquely target the spike to achieve high-affinity and broadly neutralizing activity against the evolving virus. Our study will inform the rational design of novel pan-coronavirus vaccines and therapeutics. |
リンク | bioRxiv / PubMed:33758850 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 - 3.8 Å |
構造データ | EMDB-24253, PDB-7n9a: EMDB-24255: SARS-CoV-2 S with NB21 nanobody EMDB-24256, PDB-7n9c: EMDB-24257, PDB-7n9e: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / CovS NB21 nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / CovS NB34 nanobody |