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结构分析 SARS-CoV-2 刺突蛋白的中和表位以指导治疗和疫苗设计策略。

Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.

机构信息

Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA.

出版信息

Viruses. 2021 Jan 19;13(1):134. doi: 10.3390/v13010134.

DOI:10.3390/v13010134
PMID:33477902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7833398/
Abstract

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

摘要

由于新型严重急性呼吸系统综合症冠状病毒(nCoV 或 SARS-CoV-2)引起的 COVID-19 大流行,冠状病毒研究受到了极大的关注。在这篇综述中,我们强调了最近的研究,这些研究提供了对抗 SARS-CoV-2 的单克隆抗体(mAbs)的开发具有重要意义的原子分辨率结构细节,这些 mAbs 可用于治疗和预防用途,并可用于疫苗。对 SARS-CoV-2 中和 mAbs 的结构研究揭示了 Spike 的受体结合域和 N 端结构域上多样化的结合模式,并突出了 Spike 上的替代靶标。我们将这些结构研究与体内 mAb 效应结合起来,以提示结构与临床应用之间的相关性。我们还将针对严重急性呼吸系统综合症(SARS)和中东呼吸系统综合症(MERS)冠状病毒的 mAbs 置于 SARS-CoV-2 Spike 的背景下,以提示可能需要设计 mAbs 或疫苗来赋予广泛保护的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/51adfe3643a5/viruses-13-00134-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/89b8c47f7ad8/viruses-13-00134-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/a4db4ce82946/viruses-13-00134-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/10e1dffe5dad/viruses-13-00134-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/51adfe3643a5/viruses-13-00134-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/89b8c47f7ad8/viruses-13-00134-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/a4db4ce82946/viruses-13-00134-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/10e1dffe5dad/viruses-13-00134-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a51/7833398/51adfe3643a5/viruses-13-00134-g004.jpg

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