Heparan sulfate-binding sites (HSBS)

Heparan sulfate-binding sites (HSBS) are functional domains located on various viral glycoproteins and host cell surface proteoglycans that mediate the initial attachment of viruses to host cells. These sites consist of clusters of positively charged amino acids that interact electrostatically with the negatively charged sulfate groups of heparan sulfate (HS) chains (Cagno et al., 2019). For many viruses, including SARS-CoV-2, HIV-1, and Herpes Simplex Virus, HSBS serve as essential attachment receptors that concentrate the virus on the cell surface and facilitate subsequent binding to high-affinity entry receptors (Clausen et al., 2020). On the host side, heparan sulfate proteoglycans (HSPGs) like syndecans and glypicans act as the primary docking platforms (Gallagher, 2015). Therapeutic strategies targeting these sites involve the use of HS mimetics or polyanionic compounds, such as pixatimod or suramin, which competitively inhibit the virus-HS interaction (Karamanos et al., 2018). While promising as broad-spectrum antivirals, drugs targeting HSBS must be carefully designed to avoid interfering with the critical physiological roles of HS in growth factor signaling and blood coagulation (Gallagher, 2015).

Other names

Heparan sulfate-binding domainsHS-binding sitesHeparin-binding domainsHSPG-binding sitesHeparan sulfate-binding motifs

Competitive inhibition of the electrostatic interaction between viral attachment proteins and host cell surface heparan sulfate proteoglycans, thereby preventing viral docking and subsequent membrane fusion or endocytosis (Cagno et al., 2019; Clausen et al., 2020).