Heparin-Induced Allosteric Changes in SARS-CoV-2 Spike Protein Facilitate ACE2 Binding and Viral Entry

Understanding the entry of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) into host cells is crucial in the battle against COVID-19. Using atomic force microscopy (AFM), we probed the interaction between the virus's spike protein and heparan sulfate (HS) as a potential attachment factor. Our AFM studies revealed a moderate-affinity interaction between the spike protein and HS on both model surfaces and living cells, highlighting HS's role in early viral attachment. Remarkably, we observed an interplay between HS and the host cell receptor angiotensin-converting enzyme 2 (ACE2), with HS engagement resulting in enhanced ACE2 binding and subsequent viral entry. Our research furthers our understanding of SARS-CoV-2 infection mechanisms and reveals potential interventions targeting viral entry. These insights are valuable as we navigate the evolving landscape of viral threats and seek effective strategies to combat emerging infectious diseases.