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- Yu, Mingjia, et al.
(författare)
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Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins : An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 7
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Forskningsöversikt (refereegranskat)abstract
- Owing to the high mortality and the spread rate, the infectious disease caused by SARS-CoV-2 has become a major threat to public health and social economy, leading to over 70 million infections and 1. 6 million deaths to date. Since there are currently no effective therapeutic or widely available vaccines, it is of urgent need to look for new strategies for the treatment of SARS-CoV-2 infection diseases. Binding of a viral protein onto cell surface heparan sulfate (HS) is generally the first step in a cascade of interaction that is required for viral entry and the initiation of infection. Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation. Thus, structurally defined heparin/HS and their mimetics might serve as potential drugs by competing with cell surface HS for the prevention of viral adhesion and modulation of inflammatory reaction. In this review, we will elaborate coronavirus invasion mechanisms and summarize the latest advances in HS-protein interactions, especially proteins relevant to the process of coronavirus infection and subsequent inflammation. Experimental and computational techniques involved will be emphasized.
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| 2. |
- Zhang, Tianji, et al.
(författare)
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Oligosaccharides mapping of nitrous acid degraded heparin through UHPLC-HILIC/WAX-MS
- 2020
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Building blocks characterization is a significant approach for understanding the molecular structure of heparin and its derivatives. Nitrous acid (HONO) depolymerization of heparin generates oligosaccharides that maintain the epimerization conformation on C5 of the uronic acids, reflecting the authentic structure of the parental chain. HONO treatment at pH 1.5 selectively cleaves the bond between N-sulfated glucosamine and hexuronic acid, resulting mainly disaccharides, as well as tetra-, tri-, and mono-saccharides. The tetrasaccharides are derived from the structure of N-acetylated domains while tri-, and mono-saccharides are derived from the reducing or the non-reducing end of the heparin chain. The resulted oligosaccharides were separated and analyzed using a UHPLC-HILIC/WAX-MS method. We succeeded in the identification of 19 tetrasaccharides, 19 trisaccharides and 4 monosaccharides species, majority of which is structurally characterized. By comparing the theoretical possibilities and actual occurrence of the well-characterized tetrasaccharides, we demonstrated that the biosynthesis of heparin is a systematic process.
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