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Related Concept Videos

Coronavirus01:29

Coronavirus

Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...

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Engineered Multivalent Nanobodies Potently and Broadly Neutralize SARS-CoV-2 Variants.

Jennifer M Zupancic1,2, John S Schardt1,2,3, Alec A Desai1,2

  • 1Department of Chemical Engineering University of Michigan Ann Arbor MI 48109 USA.

Advanced Therapeutics
|September 13, 2021
PubMed
Summary

Multivalent nanobodies targeting conserved SARS-CoV-2 spike protein regions show enhanced neutralization against variants. This engineering approach improves antibody efficacy for potential COVID-19 therapies.

Keywords:
COVID‐19antibodyantibody fragmentcamelidpolyvalencypolyvalentprotein engineering

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Area of Science:

  • Immunology
  • Virology
  • Biotechnology

Background:

  • The COVID-19 pandemic persists, driven by SARS-CoV-2 variants that can evade existing immunity.
  • Broadly neutralizing antibodies targeting conserved epitopes are crucial for effective COVID-19 therapeutics and prophylaxis.
  • Nanobodies offer a potential platform for developing novel antiviral agents.

Purpose of the Study:

  • To enhance the neutralizing activity of a SARS-CoV nanobody (VHH-72) against SARS-CoV-2 variants using multivalent engineering.
  • To investigate the epitope specificity of synergistic neutralization improvements.
  • To assess the therapeutic potential of multivalent VHH-72 nanobodies against SARS-CoV-2 variants.

Main Methods:

  • A multivalent engineering strategy was applied to a SARS-CoV cross-reactive nanobody (VHH-72).
  • The neutralizing activity of engineered nanobodies against SARS-CoV-2 variants (B.1.1.7, B.1.351) was evaluated.
  • Biophysical properties including stability, solubility, and non-specific binding were assessed.

Main Results:

  • Multivalent engineering of VHH-72 resulted in synergistic improvements in neutralizing activity.
  • Hexavalent VHH-72 nanobodies effectively bound and neutralized SARS-CoV-2 variants (B.1.1.7, B.1.351).
  • Engineered nanobodies exhibited favorable drug-like biophysical properties (high stability, solubility, low non-specific binding).

Conclusions:

  • Multivalent VHH-72 nanobodies demonstrate potent neutralization of SARS-CoV-2 variants.
  • The engineering approach yields nanobodies with improved therapeutic potential against current and emerging variants.
  • These multivalent nanobodies represent promising candidates for COVID-19 therapy and prophylaxis.