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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...

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Engineering Two-Dimensional Nanobody-Origami Architectures for Enhanced Antiviral Activity.

Tingjie Song1,2,3, Jazmin Galván Achi4, Varada Anirudhan4

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Summary
This summary is machine-generated.

Researchers developed a DNA origami platform to precisely arrange nanobodies (Nb) for potent antiviral therapies. This nanoscale engineering significantly boosted viral binding and neutralization against SARS-CoV-2 and HIV-1.

Keywords:
Designer DNA nanoarchitectureMultivalencyNanobodyPattern matchingViral inhibitor

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Area of Science:

  • Nanotechnology
  • Virology
  • Immunology

Background:

  • Nanoscale organization of binding ligands is a key strategy for combating viral infections.
  • Multivalent nanobodies (Nb) show promise as antiviral agents.
  • Controlling the spatial arrangement of Nbs is crucial for enhancing their efficacy.

Purpose of the Study:

  • To develop a programmable 2D DNA origami platform for nanoscale control of multivalent Nb spatial patterns.
  • To engineer origami-Nb nanoarchitectures with rationally designed Nb patterns for broad-spectrum antiviral applications.
  • To evaluate the impact of Nb spatial patterns on viral binding affinity and neutralization potency.

Main Methods:

  • Utilized a 2D DNA origami platform for programmable spatial positioning of Nbs.
  • Employed site-selective Nb-DNA conjugation for precise Nb attachment.
  • Synthesized origami-Nb nanoarchitectures with Nb patterns designed to mimic viral surface protein geometry.
  • Tested the efficacy of engineered nanoarchitectures against SARS-CoV-2 and HIV-1.

Main Results:

  • Achieved nanoscale control over Nb spatial patterns on a 2D DNA origami platform.
  • Demonstrated significantly enhanced viral binding affinity and neutralization potency with optimized Nb configurations.
  • For SARS-CoV-2, a triangular Nb pattern achieved an IC50 of 1.52 nM, a 171-fold improvement over monomeric Nbs.
  • For HIV-1, an optimal Nb pattern increased neutralization efficiency by 233-fold.

Conclusions:

  • The programmable 2D DNA origami platform enables precise nanoscale control of Nb spatial patterns.
  • Spatially optimized Nb patterns lead to significantly enhanced viral binding and neutralization.
  • This generalizable strategy offers a promising approach for engineering potent antiviral inhibitors targeting viral surface antigens.