journal article·2026-01-21

DNA Nanostructure-Mediated Bispecific Aptamers Enable Multiepitope Recognition and Robust Viral Neutralization

Qiaoyi Wu, Yihao Huang, Siyin Kang, Miao Sun, Lin Zhu, Chaoyong Yang, Yanling Song, Mengjiao Huang

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Abstract

Viral evolution through mutation often enhances infectivity and facilitates escape from existing therapeutics, highlighting the urgent need for robust strategies that can neutralize key viral proteins despite sequence variation. Here, we present a bispecific neutralizing aptamer, Aptx2-L, which simultaneously engages two distinct epitopes on the receptor-binding domain (RBD) of SARS-CoV-2. This dual-epitope recognition confers robustness against single-point mutations, reducing the risk of viral escape, while cooperative binding at separate sites synergistically enhances thermodynamic affinity. Anchoring the aptamers on a DNA framework further allows precise control of interaptamer spacing and spatial orientation, ensuring optimal geometric presentation and maximal binding efficiency. By synergistically binding, Aptx2-L demonstrates nanomolar binding affinity to RBD and potent inhibition of both wild-type and mutant SARS-CoV-2 pseudovirus infection of cells, outperforming cocktails of monospecific aptamers. Beyond SARS-CoV-2, this bispecific, multiepitope recognition strategy establishes a generalizable platform for targeting mutable proteins and other therapeutically relevant biomolecules where multisite engagement is essential, offering broad potential for molecular diagnostics and therapeutic development.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · DNA and Nucleic Acid Chemistry · RNA and protein synthesis mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Trauma Center and Emergency Surgery, the First Affiliated Hospital of Fujian Medical University

Fujian Medical University

Department of Trauma Center & Emergency Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory

Xiamen University

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, College of Chemistry and Pharmacy

Guangxi Normal University

Funding

Fujian Provincial Department of Science and Technology · Ministry of Science and Technology of the People's Republic of China · Science and Technology Department of Guangxi Zhuang Autonomous Region · China Postdoctoral Science Foundation · Ministry of Education of the People's Republic of China · Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University · Provincial Health Technology Project

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