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Controlling the Sulfation Density of Glycosaminoglycan Glycopolymer Mimetics Enables High Antiviral Activity against SARS-CoV-2 and Reduces Anticoagulant Activity

Hoffmann et al., Biomacromolecules, doi:10.1021/acs.biomac.5c00576, Jul 2025
https://c19early.org/hoffmann3.html
In Vitro study showing the efficacy of carrageenan (used as a positive control) in inhibiting SARS-CoV-2 infection. Authors preincubated SARS-CoV-2 pseudovirus (PsV) with carrageenan before infecting Vero cells. Carrageenan reduced viral infection in a concentration-dependent manner, with significant inhibition at concentrations as low as 0.01 mg/mL, outperforming heparin. The study also highlights the importance of sulfation in enhancing antiviral effects, as non-sulfated polymers failed to show significant antiviral activity. The study focuses on sulfated glycosaminoglycan (sGAG) glycopolymer mimetics with controlled sulfation density, which showed high antiviral activity against SARS-CoV-2 while reducing anticoagulant activity.
18 preclinical studies support the efficacy of iota-carrageenan for COVID-19:
Hoffmann et al., 6 Jul 2025, peer-reviewed, 10 authors. Contact: schelhaas@unimuenster.de, laura.hartmann@makro.uni-freiburg.de.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Controlling the Sulfation Density of Glycosaminoglycan Glycopolymer Mimetics Enables High Antiviral Activity against SARS-CoV-2 and Reduces Anticoagulant Activity
Miriam Hoffmann, Lorand Bonda, Ines Fels, Darisuran Anhlan, Eike Hrincius, Derik Hermsen, Stephan Ludwig, Mario Schelhaas, Nicole L Snyder, Laura Hartmann
Biomacromolecules, doi:10.1021/acs.biomac.5c00576
Sulfated glycosaminoglycans (sGAGs) make up a class of cell-surface glycans known to mediate pathogen engagement. Glycopolymers mimicking sGAGs can reduce or prevent pathogen attachment. However, their high anticoagulant activity limits their biomedical applications. Here, we report the synthesis and evaluation of synthetic glycopolymers mimicking sGAGs with high antiviral activity but low anticoagulant activity. The key lies in the control of the density of carbohydrates presented along the polymeric backbone. This was accomplished via copolymerization of carbohydrate with noncarbohydrate monomers. We reveal that the polymer chain length affects inhibition of SARS-CoV-2 pseudovirus (PsV) and authentic virus infections, and that above a critical chain length, density of carbohydrate and sulfate groups can be reduced, maintaining high antiviral activity while minimizing anticoagulant activity. This demonstrates, for the first time, how specific structural parameters of glycopolymers can be used to maximize inhibition while minimizing anticoagulative properties unlocking the full potential of sGAG mimetics in fighting infections.
Authors Miriam Hoffmann -Department of Organic Notes The authors declare no competing financial interest.
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DOI record: { "DOI": "10.1021/acs.biomac.5c00576", "ISSN": [ "1525-7797", "1526-4602" ], "URL": "http://dx.doi.org/10.1021/acs.biomac.5c00576", "alternative-id": [ "10.1021/acs.biomac.5c00576" ], "author": [ { "ORCID": "https://orcid.org/0000-0001-7709-5886", "affiliation": [ { "name": "Department of Organic and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, Düsseldorf 40225, Germany" } ], "authenticated-orcid": true, "family": "Hoffmann", "given": "Miriam", "sequence": "first" }, { "affiliation": [ { "name": "Department of Organic and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, Düsseldorf 40225, Germany" } ], "family": "Bonda", "given": "Lorand", "sequence": "additional" }, { "affiliation": [ { "name": "Institute of Cellular Virology, ZMBE and Cells in Motion Interfaculty Centre CiMIC", "place": [ "Münster, Germany" ] }, { "name": "University of Münster", "place": [ "Münster, Germany" ] } ], "family": 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