Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

Abstract

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.

Glycopolymers against pathogen infection

“…[99][100][101] Here, we highlight the review by Bianculli et 104 and a review from our own group on polymers inspired by heparin and heparan sulfate and their use in antiviral therapy. 9 The following section will therefore only highlight very recent studies from the years 2020-2022 to complement these previous review articles.…”

“…In proteoglycans, the key glycan motifs are sulfated polysaccharide chains. 9 In mucins, the focus is mostly on the terminal SiA motifs, which are also found in glycolipids such as the gangliosides or BGAs. SiA presenting glycans have been recognized as attachment factors or receptors for a great variety of viruses, the most prominent example being the influenza A virus strains.…”

“…A recent example is the GAG-mediated cell attachment of SARS-CoV-2. 9 Other glycan structures are also known to mediate pathogen interactions. For example, bacteria present pili or fimbriae, 10 hair-like protein structures that they use for attachment to the host tissue and in biofilm formation.…”

“…99–101 Here, we highlight the review by Bianculli et al from the Schulze group on antiviral polymers, 102 a review by Huang et al from the Ding group on antiviral biomaterials, 103 a review by Jung et al from the Boyer group on bioactive polymers including antiviral and antibacterial polymers 104 and a review from our own group on polymers inspired by heparin and heparan sulfate and their use in antiviral therapy. 9 The following section will therefore only highlight very recent studies from the years 2020–2022 to complement these previous review articles.…”

Amphiphilic Sulfonated Polycarbonates Inactivate SARS-CoV-2 in Seconds

“…This class of viruses infect host cells by binding of the spike protein to cellular entry receptors such as angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-CoV-2. , Upon attachment, viruses enter cells via endocytosis and subsequently replicate their RNA . By developing polymers that bind to the viral spike glycoprotein, viral attachment onto the cell receptors could be prevented effectively. , Anionic polymers were shown to be potential candidates, − as the computational ligand docking analysis provided evidence that heparan sulfate interacted with the spike glycoprotein of SARS-CoV-2. − From the safety perspective, anionic polymers usually also show lower cytotoxicity and higher biocompatibility than their cationic counterparts, partly due to the stronger interaction of cationic polymers with serum proteins in the in vivo environment. , Most antiviral polymers currently available are not easily degraded in a physiological environment, , resulting in bioaccumulation that may lead to a health and environmental concern. With a highly biocompatible and biodegradable backbone, polycarbonates therefore represent an attractive class of polymers for biological applications. − …”