三聚体
适体
DNA
中和
中和抗体
生物物理学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
化学
纳米技术
材料科学
2019年冠状病毒病(COVID-19)
生物
病毒
病毒学
遗传学
二聚体
生物化学
医学
有机化学
疾病
病理
传染病(医学专业)
作者
Shuang Wan,Siwen Liu,Miao Sun,Jialü Zhang,Xinyu Wei,Tieying Song,Yuhao Li,Xinyang Liu,Honglin Chen,Chaoyong Yang,Yanling Song
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-09-08
卷期号:16 (9): 15310-15317
被引量:11
标识
DOI:10.1021/acsnano.2c06803
摘要
Natural ligand–receptor interactions that play pivotal roles in biological events are ideal models for design and assembly of artificial recognition molecules. Herein, aiming at the structural characteristics of the spike trimer and infection mechanism of SARS-CoV-2, we have designed a DNA framework-guided spatial-patterned neutralizing aptamer trimer for SARS-CoV-2 neutralization. The ∼5.8 nm tetrahedral DNA framework affords precise spatial organization and matched valence as four neutralizing aptamers (MATCH-4), which matches with nanometer precision the topmost surface of SARS-CoV-2 spike trimer, enhancing the interaction between MATCH-4 and spike trimer. Moreover, the DNA framework provides a dimensionally complementary nanoscale barrier to prevent the spike trimer–ACE2 interaction and the conformational transition, thereby inhibiting SARS-CoV-2–host cell fusion and infection. As a result, the spatial- and valence-matched MATCH-4 ensures improved binding affinity and neutralizing activity against SARS-CoV-2 and its varied mutant strains, particularly the current Omicron variant, that are evasive of the majority of existing neutralizing antibodies. In addition, because neutralizing aptamers specific to other targets can be evolved and assembled, the present design has the potential to inhibit other wide-range and emerging pathogens.
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