化学
表面等离子共振
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
生物物理学
冠状病毒
2019年冠状病毒病(COVID-19)
DNA
病毒
病毒学
单体
结合
病毒进入
血浆蛋白结合
中和
生物化学
纳米颗粒
纳米技术
病毒复制
传染病(医学专业)
聚合物
疾病
有机化学
数学
材料科学
数学分析
生物
医学
病理
作者
Tingjie Song,Laura Cooper,Jazmin Galván Achi,Xiaojing Wang,Abhisek Dwivedy,Lijun Rong,Xing Wang
摘要
Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called “PNS”, is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained binding ability to SARS-CoV-2 spike protein and then coalescing the ssDNA–Nb conjugates around a gold nanoparticle (AuNP) via DNA hybridization with a desired Nb density that offers spatial pattern-matching with that of the Nb binding sites on the trimeric spike. The surface plasmon resonance (SPR) assays show that the PNS binds the SARS-CoV-2 trimeric spike proteins with a ∼1000-fold improvement in affinity than that of monomeric Nbs. Furthermore, our viral entry inhibition assays using the PNS against SARS-CoV-2 WA/2020 and two recent variants of interest (BQ1.1 and XBB) show an over 400-fold enhancement in viral inhibition compared to free Nbs. Our PNS strategy built on a new DNA–protein conjugation chemistry provides a facile approach to developing robust virus inhibitors by using a corresponding virus-targeting Nb with a desired Nb density.
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