Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type...

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Autores principales: Kwon, Paul S., Xu, Shirley, Oh, Hanseul, Kwon, Seok-Joon, Rodrigues, Andre L., Feroz, Maisha, Fraser, Keith, He, Peng, Zhang, Fuming, Hong, Jung Joo, Linhardt, Robert J., Dordick, Jonathan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082822/
https://www.ncbi.nlm.nih.gov/pubmed/37031303
http://dx.doi.org/10.1038/s42003-023-04789-z
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author Kwon, Paul S.
Xu, Shirley
Oh, Hanseul
Kwon, Seok-Joon
Rodrigues, Andre L.
Feroz, Maisha
Fraser, Keith
He, Peng
Zhang, Fuming
Hong, Jung Joo
Linhardt, Robert J.
Dordick, Jonathan S.
author_facet Kwon, Paul S.
Xu, Shirley
Oh, Hanseul
Kwon, Seok-Joon
Rodrigues, Andre L.
Feroz, Maisha
Fraser, Keith
He, Peng
Zhang, Fuming
Hong, Jung Joo
Linhardt, Robert J.
Dordick, Jonathan S.
author_sort Kwon, Paul S.
collection PubMed
description SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant (B.1.1.529) when compared to wild type and Delta (B.1.617.2) variants in vitro. These results suggest that inhibition of live virus infection occurs through dual SARS-CoV-2 targets of S-protein binding and previously reported RNA-dependent RNA polymerase inhibition and offers the possibility for this and other polysulfated molecules to be used as potential therapeutic and prophylactic options against COVID-19.
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spelling pubmed-100828222023-04-10 Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions Kwon, Paul S. Xu, Shirley Oh, Hanseul Kwon, Seok-Joon Rodrigues, Andre L. Feroz, Maisha Fraser, Keith He, Peng Zhang, Fuming Hong, Jung Joo Linhardt, Robert J. Dordick, Jonathan S. Commun Biol Article SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant (B.1.1.529) when compared to wild type and Delta (B.1.617.2) variants in vitro. These results suggest that inhibition of live virus infection occurs through dual SARS-CoV-2 targets of S-protein binding and previously reported RNA-dependent RNA polymerase inhibition and offers the possibility for this and other polysulfated molecules to be used as potential therapeutic and prophylactic options against COVID-19. Nature Publishing Group UK 2023-04-08 /pmc/articles/PMC10082822/ /pubmed/37031303 http://dx.doi.org/10.1038/s42003-023-04789-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kwon, Paul S.
Xu, Shirley
Oh, Hanseul
Kwon, Seok-Joon
Rodrigues, Andre L.
Feroz, Maisha
Fraser, Keith
He, Peng
Zhang, Fuming
Hong, Jung Joo
Linhardt, Robert J.
Dordick, Jonathan S.
Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title_full Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title_fullStr Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title_full_unstemmed Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title_short Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions
title_sort suramin binds and inhibits infection of sars-cov-2 through both spike protein-heparan sulfate and ace2 receptor interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082822/
https://www.ncbi.nlm.nih.gov/pubmed/37031303
http://dx.doi.org/10.1038/s42003-023-04789-z
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