DataVXSmallPaper
journal article·2025-08Open access

Polysialosides Outperform Sulfated Analogs for Binding with SARS‐CoV‐2

Vinod Khatri, Nico Boback, Hassan Abdelwahab, Daniela Niemeyer, Tahlia M. Palmer, Anil Kumar Sahoo, Yannic Kerkhoff, Kai Ludwig, Julian Heinze, Dilara Balci, Jakob Trimpert, Rainer Haag, Tatyana L. Povolotsky, Roland R. Netz, Christian Drosten, Daniel C. Lauster, Sumati Bhatia

Small· Volume 21· Issue 34
Publisher pageOpen full text
Source abstract

Abstract

Abstract Both polysialosides and polysulfates are known to interact with the receptor binding domain (RBD) of the SARS‐CoV‐2 spike protein. However, a comprehensive site by site analysis of their binding affinities and potential synergistic antiviral effects have not been performed. Here, we report on the synthesis of polysialosides with nanomolar binding affinities to spike proteins of SARS‐CoV‐2 in solution using microscale thermophoresis. The dendritic polyglycerol based polysialosides dPG500SA0.55 and dPG500SA0.25, with a dissociation constant Kd of 4.78 nm and 10.85 nm, respectively, bind ≈500 times stronger than the high density polysulfated analog dPG500S0.55, to intact SARS‐CoV‐2 virus particles or isolated spike protein. In fact, the presence of sulfate groups in a heteromultivalent compound dPG500SA0.20S0.20 weakens the binding to spike proteins. A polycarboxylated analog does not bind to SARS‐CoV‐2, ruling out that the interaction of polysialoside is simply driven by electrostatics. Using explicit‐solvent all‐atom molecular dynamics simulations and ensemble docking studies, atomistic details are obtained on the interaction of different functional groups with the SARS‐CoV‐2 RBD. The data support the conclusion that sialosides interact stronger than sulfates for their binding with RBD of SARS‐CoV‐2. Notably, the most affine binder dPG500SA0.55 inhibits SARS‐CoV‐2 (WT, D614G) replication up to 98.6% at 0.5 µm concentrations.
Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Advanced Chemical Sensor Technologies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Freie Universität Berlin Institute of Chemistry and Biochemistry Takustr. 3 14195 Berlin Germany

Department of Chemistry TDL Govt. College for Women Murthal Sonipat Haryana 131027 India

Freie Universität Berlin Institute of Pharmacy, Biopharmaceuticals Kelchstr. 31 12169 Berlin Germany

Freie Universität Berlin SupraFAB, Department of Biology, Chemistry and Pharmacy, and Department of Physics Altensteinstr. 23a 14195 Berlin Germany

Freie Universität Berlin Department of Physics Arnimallee 14 14195 Berlin Germany

Institute of Virology, Campus Berlin Mitte Charité – Universitätsmedizin Berlin Charitéplatz 1 10117 Berlin Germany

Freie Universität Berlin Forschungszentrum für Elektronenmikroskopie, Core‐Facility BioSupraMol, Institute of Chemistry and Biochemistry Fabeckstraße 36a 14195 Berlin Germany

IT & Data Services Zuse Institute Berlin Takustraße 7 14195 Berlin Germany

Department of Pathobiology and Diagnostic Medicine Kansas State University 1800 Denison Avenue Manhattan KS 66506 USA

Department of Chemistry, Faculty of Science and Engineering Swansea University Singleton Campus Swansea SA2 8PP United Kingdom

Funding

Bundesministerium für Bildung und Forschung · Berlin University Alliance · Royal Society of Chemistry · Deutsche Forschungsgemeinschaft

References (50)

Show source-provided references
1. WHO COVID‐19 epidemiological update – World Health Organization2024 pp1 https://www.who.int/publications/m/item/covid‐19‐epidemiological‐update‐edition‐172.
2. 10.1016/j.str.2020.10.00110.1016/j.str.2020.10.001 ↗
3. 10.1126/science.abb276210.1126/science.abb2762 ↗
4. 10.3389/fmicb.2023.116954710.3389/fmicb.2023.1169547 ↗
5. 10.1038/s41421-020-00192-810.1038/s41421-020-00192-8 ↗
6. 10.1016/j.cell.2020.09.03310.1016/j.cell.2020.09.033 ↗
7. 10.1126/scitranslmed.adi262310.1126/scitranslmed.adi2623 ↗
8. 10.1002/anie.20210271710.1002/anie.202102717 ↗
9. 10.1371/journal.ppat.101059010.1371/journal.ppat.1010590 ↗
10. 10.1038/s41589-021-00924-110.1038/s41589-021-00924-1 ↗
11. 10.1021/acscentsci.0c0085510.1021/acscentsci.0c00855 ↗
12. 10.1038/s41467-022-30313-810.1038/s41467-022-30313-8 ↗
13. 10.1016/j.biomaterials.2017.05.02810.1016/j.biomaterials.2017.05.028 ↗
14. 10.1002/adma.20240829410.1002/adma.202408294 ↗
15. 10.1021/acs.nanolett.3c0040810.1021/acs.nanolett.3c00408 ↗
16. 10.1021/jm00114a02510.1021/jm00114a025 ↗
17. 10.1016/j.molstruc.2014.03.00910.1016/j.molstruc.2014.03.009 ↗
18. 10.3389/fmedt.2020.61465210.3389/fmedt.2020.614652 ↗
19. 10.1016/j.csbj.2022.11.00410.1016/j.csbj.2022.11.004 ↗
20. 10.1126/science.abm312510.1126/science.abm3125 ↗
21. 10.1126/sciadv.adk492010.1126/sciadv.adk4920 ↗
22. 10.1002/anie.20220143210.1002/anie.202201432 ↗
23. 10.3389/fchem.2021.65976410.3389/fchem.2021.659764 ↗
24. 10.1080/07391102.2023.223404410.1080/07391102.2023.2234044 ↗
25. 10.1021/acs.jpcb.3c0625810.1021/acs.jpcb.3c06258 ↗
26. 10.1021/acscentsci.0c0105610.1021/acscentsci.0c01056 ↗
27. 10.1002/cbic.20210068110.1002/cbic.202100681 ↗
28. 10.1021/jacsau.4c0088610.1021/jacsau.4c00886 ↗
29. 10.1128/JVI.01358-0610.1128/JVI.01358-06 ↗
30. 10.1093/bioinformatics/btx18010.1093/bioinformatics/btx180 ↗
31. 10.26434/chemrxiv‐2024‐8b0gb10.26434/chemrxiv‐2024‐8b0gb ↗
32. 10.1002/jcc.2094510.1002/jcc.20945 ↗
33. 10.1002/jcc.2136710.1002/jcc.21367 ↗
34. 10.1002/jcc.2306710.1002/jcc.23067 ↗
35. 10.1021/ci300363c10.1021/ci300363c ↗
36. 10.1021/ci300364910.1021/ci3003649 ↗
37. 10.1038/nmeth.406710.1038/nmeth.4067 ↗
38. 10.1063/1.44586910.1063/1.445869 ↗
39. 10.1021/jp401512z10.1021/jp401512z ↗
40. 10.1016/j.softx.2015.06.00110.1016/j.softx.2015.06.001 ↗
41. 10.1063/1.240842010.1063/1.2408420 ↗
42. 10.1063/1.32869310.1063/1.328693 ↗
43. 10.1021/ct700200b10.1021/ct700200b ↗
44. 10.1063/1.46439710.1063/1.464397 ↗
45. 10.1002/jcc.2133410.1002/jcc.21334 ↗
46. 10.1186/1758-2946-4-1710.1186/1758-2946-4-17 ↗
47. 10.1093/nar/gkab29410.1093/nar/gkab294 ↗
48. 10.2807/1560-7917.ES.2020.25.3.200004510.2807/1560-7917.ES.2020.25.3.2000045 ↗
49. 10.1371/journal.pbio.300187110.1371/journal.pbio.3001871 ↗
50. 10.1016/j.cell.2020.09.04910.1016/j.cell.2020.09.049 ↗