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  Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions

Nie, C., Pouyan, P., Lauster, D., Trimpert, J., Kerkhoff, Y., Szekeres, G. P., et al. (2021). Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions. Angewandte Chemie International Edition, 60(29), 15870-15878. doi:10.1002/anie.202102717.

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 Creators:
Nie, Chuanxiong1, 2, Author
Pouyan, Paria1, Author
Lauster, Daniel1, Author
Trimpert, Jakob2, Author
Kerkhoff, Yannic3, Author
Szekeres, Gergő Péter1, 4, Author           
Wallert, Matthias3, Author
Block, Stephan3, Author
Sahoo, Anil Kumar5, 6, Author
Dernedde, Jens7, Author
Pagel, Kevin1, 4, Author           
Kaufer, Benedikt B.2, Author
Netz, Roland R.5, Author
Ballauff, Matthias1, Author
Haag, Rainer1, Author
Affiliations:
1Institut für Chemie und Biochemie, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany, ou_persistent22              
2Free Univ Berlin, Inst Virol, Robert von Ostertag Str 7-13, D-14163 Berlin, Germany, ou_persistent22              
3Free Univ Berlin, Dept Chem & Biochem, Emmy Noether Grp Bionanointerfaces, Arnimallee 22, D-14195 Berlin, Germany, ou_persistent22              
4Molecular Physics, Fritz Haber Institute, Max Planck Society, ou_634545              
5Free Univ Berlin, Fachbereich Phys, Arnimallee 14, D-14195 Berlin, Germany, ou_persistent22              
6Max Planck Inst Colloids & Interfaces, Muhlenberg 1, D-14476 Potsdam, Germany, ou_persistent22              
7Charite Univ Med Berlin, Klin Chem & Pathobiochem, Inst Lab Med, Augustenburgerpl 1, D-13353 Berlin, Germany, ou_persistent22              

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Free keywords: polysulfates; SARS-CoV-2; inhibition; virus binding; electrostatic interactions
 Abstract: Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC50) of 67 μg/mL (approx.1.6 μM). This synthetic polysulfates exhibit more than 60-fold higher virus inhibitory activity than heparin (IC50: 4084μg/mL), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind stronger to the spike protein than heparin, and that LPGS can interact even morewith the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interaction, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.

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Language(s): eng - English
 Dates: 2021-02-232021-04-162021-04-162021-07-12
 Publication Status: Issued
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/anie.202102717
 Degree: -

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Title: Angewandte Chemie International Edition
  Abbreviation : Angew. Chem., Int. Ed.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: 9 Volume / Issue: 60 (29) Sequence Number: - Start / End Page: 15870 - 15878 Identifier: ISSN: 1433-7851