Variant-Specific Interactions at the Plasma Membrane: Heparan Sulfate’s Impact on SARS-CoV-2 Binding Kinetics
Artikel i vetenskaplig tidskrift, 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.

Författare

Dario Valter Conca

Umeå universitet

Fouzia Bano

Umeå universitet

Małgorzata Graul

Umeå universitet

Julius von Wirén

Umeå universitet

Lauriane Scherrer

Umeå universitet

Hudson Pace

Umeå universitet

Himanshu Sharma

Umeå universitet

Justas Svirelis

Chalmers, Kemi och kemiteknik, Tillämpad kemi

Konrad Thorsteinsson

Umeå universitet

Andreas Dahlin

Chalmers, Kemi och kemiteknik, Tillämpad kemi

Marta Bally

Umeå universitet

Analytical Chemistry

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

Vol. 97 8 4318-4328

Ämneskategorier (SSIF 2025)

Mikrobiologi inom det medicinska området

DOI

10.1021/acs.analchem.4c04283

PubMed

39976108

Mer information

Senast uppdaterat

2025-03-29