Our First Research Publication of 2025!

We are thrilled to kick off 2025 with the publication of our exciting results in the journal Analytical Chemistry! Congrats Dario! 🎉 🎉 🎉

Our study, “Variant-Specific Interactions at the Plasma Membrane: Heparan Sulfate’s Impact on SARS-CoV-2 Binding Kinetics,” takes a deep look into the complex nature of viral interactions at the cell surface. Using a toolbox of advanced biophysical approaches, and models of the cell surface reflecting the complex composition of the plasma membrane (e.g., native supported lipid bilayers), we characterized the evolution of interaction dynamics of the SARS-CoV-2 variants. We also showed how heparan sulfate (HS), a major component of the cell surface, influences the binding kinetics of the different SARS-CoV-2 variants.

Key findings

• Increased affinity for Omicron: Our study reveals a significant increase in the affinity of the multivalent bond of a virion mimetic to the cell surface for the Omicron variant, driven by an increased association rate.
• Role of HS: HS plays a central role in modulating the interaction with the cell surface, shifting from screening the interaction with ACE2 in early variants to becoming an important binding factor for Omicron.

The researchers behind this story

This publication is the result of a fantastic collaborative effort. Special thanks to:

• • Dario for leading the project with dedication and doing all the night-long single-particle-binding kinetics experiments with the TIRF microscope.
  • Fouzia for using her expertise in AFM single molecule force spectroscopy to complement TIRF binding kinetics data and look at individual spike-glycan interactions.
  • Two undergrad students (Julius and Lauriane) who joined this project during their time in the lab, and the others lab members for their hard work and dedication in getting all the controls and complementary experiments done.
  • our external collaborators.

Implication

Understanding the variant-specific interactions at the plasma membrane is crucial in the ongoing efforts against COVID-19. Our findings highlight the role of heparan sulfate in modulating viral binding, which could have significant implications for developing antiviral strategies.

Read the full story here!

We thank Department of Clinical Microbiology at Umea university, UCMR, Knut and Alice Wallenberg foundation (WCMM) and the funding sources including MSCA postdoctoral fellowship (Dario) and VR (Marta).

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