Structurally defined heparin octasaccharide domain for binding to SARS-CoV-2 Omicron BA.4/BA.5/BA.5.2 spike protein RBD
Copyright © 2024 Elsevier B.V. All rights reserved..
Heparin, a bio-molecule with the highest negative charge density, is pharmaceutically important to prevent SARS-CoV-2 infection due to its strong competitive binding to spike protein compared with cellular heparan sulfate, which was confirmed as a co-receptor for virus-host cell interaction. Hence, the refined structural characterization of heparin targeting viral protein-HS interaction was significant for developing antiviral pharmaceuticals. In our study, heparin oligomers (dp ≥ 4) were prepared using heparinase I. The affinity oligosaccharides binding to Omicron spike protein RBD were separated by affinity chromatography and size exclusion chromatography. HILIC-ESI-FTMS was used for chain mapping analysis. The basic building blocks were analyzed and the binding domain sequence was produced by Seq-GAG software and further measured by SAX chromatography. As results, heparin octasaccharide was found with significantly higher binding ability than hexasaccharide and tetrasaccharide, and the octasaccharide [ΔUA-GlcNS6S-GlcA-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S] with 12 sulfate groups showed high binding to RBD. The mechanism of this structurally well-defined octasaccharide binding to RBD was further investigated by molecular docking. The affinity energy of optimal pose was -6.8 kcal/mol and the basic amino acid residues in RBD sequence (Arg403, Arg452, Arg493 and His505) were identified as the major contribution factor to interacting with sulfate/carboxyl groups on saccharide chain. Our study demonstrated that heparin oligosaccharide with well-defined structure could be potentially developed as anti-SARS-CoV-2 drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:259 |
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| Enthalten in: |
International journal of biological macromolecules - 259(2024), Pt 1 vom: 29. Feb., Seite 129032 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
An, Zizhe [VerfasserIn] |
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| Links: |
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| Themen: |
9005-49-6 |
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| Anmerkungen: |
Date Completed 22.02.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2023.129032 |
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| funding: |
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| 245 | 1 | 0 | |a Structurally defined heparin octasaccharide domain for binding to SARS-CoV-2 Omicron BA.4/BA.5/BA.5.2 spike protein RBD |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Heparin, a bio-molecule with the highest negative charge density, is pharmaceutically important to prevent SARS-CoV-2 infection due to its strong competitive binding to spike protein compared with cellular heparan sulfate, which was confirmed as a co-receptor for virus-host cell interaction. Hence, the refined structural characterization of heparin targeting viral protein-HS interaction was significant for developing antiviral pharmaceuticals. In our study, heparin oligomers (dp ≥ 4) were prepared using heparinase I. The affinity oligosaccharides binding to Omicron spike protein RBD were separated by affinity chromatography and size exclusion chromatography. HILIC-ESI-FTMS was used for chain mapping analysis. The basic building blocks were analyzed and the binding domain sequence was produced by Seq-GAG software and further measured by SAX chromatography. As results, heparin octasaccharide was found with significantly higher binding ability than hexasaccharide and tetrasaccharide, and the octasaccharide [ΔUA-GlcNS6S-GlcA-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S] with 12 sulfate groups showed high binding to RBD. The mechanism of this structurally well-defined octasaccharide binding to RBD was further investigated by molecular docking. The affinity energy of optimal pose was -6.8 kcal/mol and the basic amino acid residues in RBD sequence (Arg403, Arg452, Arg493 and His505) were identified as the major contribution factor to interacting with sulfate/carboxyl groups on saccharide chain. Our study demonstrated that heparin oligosaccharide with well-defined structure could be potentially developed as anti-SARS-CoV-2 drugs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Heparin | |
| 650 | 4 | |a Octasaccharide | |
| 650 | 4 | |a Omicron | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Spike protein RBD | |
| 650 | 7 | |a Heparin |2 NLM | |
| 650 | 7 | |a 9005-49-6 |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Oligosaccharides |2 NLM | |
| 650 | 7 | |a Sulfates |2 NLM | |
| 700 | 1 | |a Bu, Changkai |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Deling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qingqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qingchi |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Lianli |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:259 |g year:2024 |g number:Pt 1 |g day:29 |g month:02 |g pages:129032 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ijbiomac.2023.129032 |3 Volltext |
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