SARS-CoV-2 spike protein–heparin interaction (SARS-CoV-2 S–heparin interaction)

The SARS-CoV-2 spike protein–heparin interaction is a critical biochemical event where the viral spike (S) protein binds to host cell surface heparan sulfate (HS) proteoglycans, which act as essential co-receptors for viral entry (Clausen et al., 2020). This interaction, primarily involving the receptor-binding domain (RBD) of the S protein, facilitates the initial attachment and concentration of the virus on the host cell membrane (Kim et al., 2020). Binding to heparan sulfate is thought to induce a conformational change in the spike protein that shifts the RBD into an "open" state, significantly enhancing its affinity for the primary entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) (Partridge et al., 2021). Heparin, a highly sulfated glycosaminoglycan and structural analog of heparan sulfate, can competitively bind to the spike protein, effectively acting as a decoy that prevents viral attachment to host cells (Mycroft-West et al., 2020). This interaction has made the spike protein–heparin interface a target for therapeutic intervention, using inhaled or systemic heparin and other heparinoids to neutralize the virus and reduce infectivity (Tandon et al., 2021). Beyond its role in viral entry, the interaction may also contribute to the systemic coagulopathy and inflammatory responses observed in severe COVID-19 cases (Hippensteel et al., 2020).

Other names

SARS-CoV-2 spike protein–heparan sulfate interactionS protein–heparin bindingSARS-CoV-2 S–HS interactionSARS-CoV-2 spike protein–glycosaminoglycan interaction

Competitive inhibition of viral attachment to host cells by acting as a decoy for cellular heparan sulfate, potentially inducing conformational changes in the spike protein that prevent ACE2 binding (Clausen et al., 2020; Mycroft-West et al., 2020).