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Updated: Aug 8, 2025

Engineering Antiviral Agents via Surface Plasmon Resonance

Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

SARS-CoV-2 S Glycoprotein Stabilization Strategies.

Borys Pedenko¹, Guidenn Sulbaran¹, Delphine Guilligay¹

¹University Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), 38000 Grenoble, France.

|February 28, 2023

Summary

Stabilizing the SARS-CoV-2 spike (S) glycoprotein in its prefusion conformation is crucial for effective vaccines. This strategy enhances the induction of neutralizing antibodies by preventing off-target epitope exposure.

Keywords:

S glycoprotein SARS-CoV-2 neutralizing antibodies stabilization vaccine virus entry

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Area of Science:

Structural biology
Virology
Immunology
Vaccine development

Background:

The SARS-CoV-2 pandemic highlighted the critical role of structural biology in understanding viral mechanisms and developing therapeutics.
The SARS-CoV-2 spike (S) glycoprotein is a primary target for neutralizing antibodies, crucial for vaccine development.
Native SARS-CoV-2 S glycoproteins exist in a metastable prefusion conformation, essential for viral entry but prone to conformational changes.

Approach:

Review of viral glycoprotein stabilization methods developed prior to SARS-CoV-2.
Application of these stabilization techniques to the SARS-CoV-2 S glycoprotein.
Focus on stabilizing the S glycoprotein in its native prefusion trimer conformation.

Key Points:

The prefusion conformation of the S glycoprotein is the primary target for neutralizing antibodies.
Conformational changes in the S glycoprotein during viral entry can expose off-target epitopes, hindering vaccine efficacy.
Stabilization methods aim to maintain the S glycoprotein in its immunologically relevant prefusion state.

Conclusions:

Stabilizing the SARS-CoV-2 S glycoprotein in its prefusion conformation is vital for effective vaccine design.
Structure-based approaches utilizing stabilized S trimers offer improved protective efficacy compared to non-stabilized S.
This strategy ensures that vaccines primarily induce antibodies targeting the native, functional conformation of the spike protein.