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Nanobody engineering for SARS-CoV-2 neutralization and detection.

Liina Hannula1, Suvi Kuivanen2, Jonathan Lasham3

  • 1Institute of Biotechnology, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.

Microbiology Spectrum
|February 16, 2024
PubMed
Summary

Engineered nanobodies offer potent neutralization of SARS-CoV-2 variants and enable rapid detection of the spike protein. This research highlights nanobody engineering

Keywords:
SARS-CoV-2diagnosticsnanobodyprotein engineeringvirus neutralization

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Area of Science:

  • Biotechnology
  • Immunology
  • Virology

Background:

  • Conventional antibodies face limitations in stability and cost for widespread therapeutic use.
  • Nanobodies, derived from camelid antibodies, present advantages such as high stability and lower production costs.
  • Emerging infectious diseases like COVID-19 necessitate innovative therapeutic and diagnostic solutions.

Purpose of the Study:

  • To engineer multimodular nanobodies for potent neutralization of SARS-CoV-2 and its variants.
  • To develop nanobody-based diagnostic tools for rapid detection of the SARS-CoV-2 spike protein.
  • To explore the potential of nanobody engineering in combating emerging viral threats.

Main Methods:

  • Engineering multimodular nanobody constructs by fusing domains targeting distinct SARS-CoV-2 epitopes.
  • Evaluating the neutralization potency of engineered nanobodies against wild-type and variant SARS-CoV-2 strains.
  • Developing a diagnostic assay by fusing nanobodies with NanoLuc luciferase fragments for spike protein detection.

Main Results:

  • Engineered multimodular nanobodies achieved high potency neutralization of wild-type SARS-CoV-2, Alpha, and Delta variants (IC50 as low as 50 pM).
  • Beta and Omicron variants showed increased resistance to neutralization, underscoring the challenge of antigenic drift.
  • A single-step assay detected sub-nanomolar quantities of SARS-CoV-2 spike protein using nanobody-luciferase fusions.

Conclusions:

  • Nanobody engineering provides a versatile platform for developing potent antiviral therapeutics.
  • Engineered nanobodies can be adapted for rapid and sensitive diagnostic tools for outbreak management.
  • This approach demonstrates significant potential for creating effective countermeasures against emerging infectious diseases.