Variant-Specific Interactions at the Plasma Membrane: Heparan Sulfateā€™s Impact on SARS-CoV-2 Binding Kinetics
Journal article, 2025

The spread of SARS-CoV-2 led to the emergence of several variants of concern (VOCs). The spike glycoprotein, responsible for engaging the viral receptor, exhibits the highest density of mutations, suggesting an ongoing evolution to optimize viral entry. This study characterizes the bond formed by virion mimics carrying the SARS-CoV-2 spike protein and the plasma membrane of host cells in the early stages of virus entry. Contrary to the traditional analysis of isolated ligand-receptor pairs, we utilized well-defined biomimetic models and biochemical and biophysical techniques to characterize the multivalent interaction of VOCs with the complex cell membrane. We observed an overall increase in the binding affinity for newer VOCs. By progressively reducing the system complexity, we identify heparan sulfate (HS) as a main driver of this variation, with a 10-fold increase in affinity for Omicron BA.1 over that of the original strain. These results demonstrate the essential role of coreceptors, particularly HS, in the modulation of SARS-CoV-2 infection and highlight the importance of multiscale biophysical and biochemical assays that account for membrane complexity to fully characterize and understand the role of molecular components and their synergy in viral attachment and entry.

Author

Dario Valter Conca

Umeå University

Fouzia Bano

Umeå University

Małgorzata Graul

Umeå University

Julius von Wirén

Umeå University

Lauriane Scherrer

Umeå University

Hudson Pace

Umeå University

Himanshu Sharma

Umeå University

Justas Svirelis

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Konrad Thorsteinsson

Umeå University

Andreas Dahlin

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Marta Bally

Umeå University

Analytical Chemistry

0003-2700 (ISSN) 1520-6882 (eISSN)

Vol. 97 8 4318-4328

Subject Categories (SSIF 2025)

Microbiology in the Medical Area

DOI

10.1021/acs.analchem.4c04283

PubMed

39976108

More information

Latest update

3/29/2025