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Spatial- and Valence-Matched Neutralizing DNA Nanostructure Blocks Wild-Type SARS-CoV-2 and Omicron Variant

Shuang Wan1, Siwen Liu2, Miao Sun1

  • 1The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

ACS Nano
|September 8, 2022
PubMed
Summary
This summary is machine-generated.

Researchers developed a DNA framework aptamer (MATCH-4) that precisely targets SARS-CoV-2 spike proteins. This aptamer neutralizes the virus, including Omicron variants, by blocking cell entry and shows potential for combating other pathogens.

Keywords:
OmicronSARS-CoV-2 neutralizationneutralizing aptamerspatial-patterned interaction; DNA nanotechnology

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Virology

Background:

  • Natural ligand-receptor interactions inform the design of artificial recognition molecules.
  • SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) spike protein structure and infection mechanisms are key targets for therapeutic intervention.

Purpose of the Study:

  • To design and synthesize a DNA framework-guided, spatial-patterned neutralizing aptamer trimer for effective SARS-CoV-2 neutralization.
  • To enhance binding affinity and neutralizing activity against SARS-CoV-2 and its variants through precise molecular assembly.

Main Methods:

  • Design of a tetrahedral DNA framework (∼5.8 nm) for precise spatial organization of four neutralizing aptamers (MATCH-4).
  • Engineering MATCH-4 to achieve nanometer-scale spatial and valence matching with the SARS-CoV-2 spike trimer surface.
  • Utilizing the DNA framework as a nanoscale barrier to inhibit spike protein-ACE2 interaction and viral fusion.

Main Results:

  • MATCH-4 demonstrated enhanced binding affinity and neutralizing activity against SARS-CoV-2, including immune-evasive variants like Omicron.
  • The spatial and valence matching of MATCH-4 to the spike trimer significantly improved its efficacy.
  • The DNA framework effectively prevented spike protein-ACE2 interaction and subsequent viral infection.

Conclusions:

  • The designed MATCH-4 aptamer is a potent SARS-CoV-2 neutralizer, effective against current variants.
  • This DNA framework-based aptamer design strategy offers a versatile platform for developing inhibitors against emerging and other viral pathogens.