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靶向 SARS-CoV-2 刺突糖蛋白受体结合域的适体的发现。

Discovery of Aptamers Targeting the Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein.

机构信息

The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

出版信息

Anal Chem. 2020 Jul 21;92(14):9895-9900. doi: 10.1021/acs.analchem.0c01394. Epub 2020 Jul 2.

Abstract

The World Health Organization has declared the outbreak of a novel coronavirus (SARS-CoV-2 or 2019-nCoV) as a global pandemic. However, the mechanisms behind the coronavirus infection are not yet fully understood, nor are there any targeted treatments or vaccines. In this study, we identified high-binding-affinity aptamers targeting SARS-CoV-2 RBD, using an ACE2 competition-based aptamer selection strategy and a machine learning screening algorithm. The values of the optimized CoV2-RBD-1C and CoV2-RBD-4C aptamers against RBD were 5.8 nM and 19.9 nM, respectively. Simulated interaction modeling, along with competitive experiments, suggests that two aptamers may have partially identical binding sites at ACE2 on SARS-CoV-2 RBD. These aptamers present an opportunity for generating new probes for recognition of SARS-CoV-2 and could provide assistance in the diagnosis and treatment of SARS-CoV-2 while providing a new tool for in-depth study of the mechanisms behind the coronavirus infection.

摘要

世界卫生组织已宣布新型冠状病毒(SARS-CoV-2 或 2019-nCoV)爆发为全球大流行。然而,冠状病毒感染的机制尚未完全阐明,也没有针对该病毒的靶向治疗方法或疫苗。在这项研究中,我们使用基于 ACE2 竞争的适体选择策略和机器学习筛选算法,鉴定出针对 SARS-CoV-2 RBD 的高结合亲和力适体。优化后的 CoV2-RBD-1C 和 CoV2-RBD-4C 适体对 RBD 的 值分别为 5.8 nM 和 19.9 nM。模拟相互作用模型以及竞争实验表明,两个适体可能在 SARS-CoV-2 RBD 的 ACE2 上具有部分相同的结合位点。这些适体为识别 SARS-CoV-2 提供了新的探针生成机会,并可在 SARS-CoV-2 的诊断和治疗中提供帮助,同时为深入研究冠状病毒感染的机制提供了新的工具。

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