Evolution of SARS-CoV-2 spike trimers towards optimized heparan sulfate cross-linking and inter-chain mobility
2024

How Omicron Spike Proteins Evolved to Bind Heparan Sulfate

publication Evidence: high

Author Information

Author(s): Froese Jurij, Mandalari Marco, Civera Monica, Elli Stefano, Pagani Isabel, Vicenzi Elisa, Garcia-Monge Itzel, Di Iorio Daniele, Frank Saskia, Bisio Antonella, Lenhart Dominik, Gruber Rudolf, Yates Edwin A., Richter Ralf P., Guerrini Marco, Wegner Seraphine V.

Primary Institution: University of Münster

Hypothesis

The increased heparan sulfate binding and decreased unbinding of SARS-CoV-2 variants would come at the expense of decreased mobility.

Conclusion

Omicron spike proteins have evolved to balance heparan sulfate interaction stability and dynamics, enhancing their mobility on heparan sulfate-functionalized surfaces.

Supporting Evidence

  • Omicron spike proteins can cross-link multiple heparan sulfate chains.
  • Enhanced binding of Omicron spike proteins to heparan sulfate was observed.
  • Omicron variant shows increased stability in binding to heparan sulfate compared to earlier variants.
  • Pharmaceutical targeting of heparan sulfate interactions can reduce Omicron infection.

Takeaway

Scientists studied how the Omicron variant of the coronavirus binds to heparan sulfate, a sugar on cell surfaces, and found that it can move better while still sticking to it.

Methodology

The study used molecular docking analyses and quartz crystal microbalance with dissipation monitoring to investigate the interactions of SARS-CoV-2 spike proteins with heparan sulfate.

Digital Object Identifier (DOI)

10.1038/s41598-024-84276-5

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