Dual ACE2 epitope-based biomimetic receptors for selective sensing of SARS-CoV variants.

Smart Biosensors: Dual ACE2 Epitope Receptors Offer Rapid Detection of SARS-CoV Variants

Next-Generation Biosensors: Dual ACE2 Epitope Technology for SARS-CoV Variant Detection

As the world continues to face rapidly evolving viral threats, the need for fast, accurate, and cost-effective diagnostic tools has never been greater. Conventional methods like PCR and sequencing, while highly sensitive, are often time-consuming and resource-intensive—a major bottleneck during pandemic surges.

A breakthrough study introduces dual ACE2 epitope-based biomimetic receptors as a next-generation sensing technology capable of detecting multiple SARS-CoV variants with high selectivity and speed, using surface plasmon resonance (SPR) biosensors.

The Science Behind Dual Epitope Biosensors

Researchers engineered peptide-based receptors mimicking the human ACE2 protein—the key entry point for coronaviruses like SARS-CoV-2.

Key innovations include:

  • Single vs. Dual Epitopes: Single-epitope sensors provided variant-specific detection, while dual-epitope sensors combined multiple binding regions, significantly enhancing sensitivity and variant adaptability.
  • Surface Plasmon Resonance (SPR): A powerful optical technique that detects molecular interactions in real time, ensuring rapid and label-free analysis.

Key Findings from the Study

  1. High Sensitivity for Multiple Variants
    • Single-epitope sensors achieved nanomolar affinity for SARS-CoV-2 Alpha, Delta, and SARS-CoV-1 variants.
    • Dual-epitope sensors further boosted binding strength, especially for SARS-CoV-1, showing up to 9-fold higher affinity than single sensors.
  2. Reversed Binding Preferences
    • While single sensors favored SARS-CoV-2 Delta, dual sensors showed superior detection for SARS-CoV-1, demonstrating tunable variant specificity.
  3. Structural Insights via Molecular Dynamics
    • Simulations revealed that dual-epitope sensors stabilized receptor structures, improving binding efficiency and mimicking natural ACE2-virus interactions.
  4. Selectivity Over Non-Target Viruses
    • Sensors showed negligible binding to the α-coronavirus HCoV-NL63, ensuring high diagnostic specificity for β-coronaviruses like SARS-CoV-2.
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Why This Matters for Future Pandemics

The study demonstrates a rapid, customizable sensor design strategy for emerging viruses:

  • Fast Response: Sensors can be engineered quickly for new variants.
  • Cost-Effective: Eliminates the need for expensive reagents and complex protocols.
  • Portable Diagnostics: SPR-based sensors could be integrated into point-of-care devices for field testing.

This approach opens the door for next-generation diagnostic platforms that combine speed, accuracy, and adaptability, crucial for managing future outbreaks.

Conclusion

By leveraging dual ACE2 epitope-based biomimetic receptors, researchers have pioneered a versatile biosensing technology capable of real-time, variant-specific viral detection.

With the ability to adapt rapidly to mutations, these sensors could revolutionize pandemic preparedness, enabling faster diagnostics and better outbreak control in the years ahead.

Reference

Al-Dujaili, T., Sigurdardóttir, S.B., Jiménez, V.A. et al. Dual ACE2 epitope-based biomimetic receptors for selective sensing of SARS-CoV variants. Sci Rep 15, 32687 (2025). https://doi.org/10.1038/s41598-025-20837-6

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