Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

Heparin (HP) and heparan sulfate (HS) are linear, anionically charged polysaccharides well-known for their diverse biological activities. While HP is generally localized in mast cells and in connective tissues, HS is part of the glycocalyx and involved in the attachment of viruses to host cells, constituting the first step of an infection. HP and HS also exhibit antiviral activity by blocking viral receptors, thereby inhibiting viruses from engaging with host cells. Inspired by their structural features, such as their high molecular weight and polyanionic character, various synthetic polymers mimicking HP/HS have been developed and used as model systems to study bioactivity, as well as for therapeutic applications. This Perspective provides an overview of the roles of HP/HS in viral engagement, and examines historical and recent approaches toward oligo-/polysaccharide, glycopolymer, and anionic polymer HP/HS mimetics. An overview of current applications and future prospects of these molecules is provided, demonstrating their potential in addressing current and future epidemics and pandemics.