The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics.

Friederike Eilts, Sarah Bauer, Keith Fraser, Jonathan S Dordick, Michael W Wolff, Robert J Linhardt, Fuming Zhang

Journal: Carbohydrate polymers 2023;299():120167

PMID: 36876764

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Abstract

In December 2019, the global coronavirus disease 2019 (COVID-19) pandemic began in Wuhan, China. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells primarily through the angiotensin-converting enzyme 2 (ACE2) receptor. In addition to ACE2, several studies have shown the importance of heparan sulfate (HS) on the host cell surface as a co-receptor for SARS-CoV-2-binding. This insight has driven research into antiviral therapies, aimed at inhibiting the HS co-receptor-binding, e.g., by glycosaminoglycans (GAGs), a family of sulfated polysaccharides that includes HS. Several GAGs, such as heparin (a highly sulfated analog of HS), are used to treat various health indications, including COVID-19. This review is focused on current research on the involvement of HS in SARS-CoV-2 infection, implications of viral mutations, as well as the use of GAGs and other sulfated polysaccharides as antiviral agents.

Address: Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen (THM), Giessen, Germany.; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.; Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.; Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen (THM), Giessen, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Giessen, Germany.; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. Electronic address: [email protected].; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. Electronic address: [email protected].

DOI: 10.1016/j.carbpol.2022.120167