SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins

Marta Bermejo-Jambrina; Julia Eder; Tanja M. Kaptein; Leanne C. Helgers; Philip J.M. Brouwer; John L. van Hamme; Alexander P.J. Vlaar; Frank E.H.P. van Baarle; Godelieve J. de Bree; Bernadien M. Nijmeijer; Neeltje A. Koostra; Marit J. van Gils; Rogier W. Sanders; Teunis B. H. Geijtenbeek

doi:https://doi.org/10.1101/2020.08.18.255810

SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins

Marta Bermejo-Jambrina, Julia Eder, Tanja M. Kaptein, Leanne C. Helgers, Philip J.M. Brouwer, John L. van Hamme, Alexander P.J. Vlaar, Frank E.H.P. van Baarle, Godelieve J. de Bree, Bernadien M. Nijmeijer, Neeltje A. Koostra, Marit J. van Gils, Rogier W. Sanders, Teunis B. H. Geijtenbeek

Research output: Contribution to journal › Article › Academic

Abstract

The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and new outbreaks worldwide highlight the need for preventive treatments. Although angiotensin converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2, we identified heparan sulfate proteoglycans expressed by epithelial cells, alveolar macrophages and dendritic cells as co-receptors for SARS-CoV-2. Low molecular weight heparins (LMWH) blocked SARS-CoV-2 infection of epithelial cells and alveolar macrophages, and virus dissemination by dendritic cells. Notably, potent neutralizing antibodies from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, underscoring the importance of heparan sulfate proteoglycans as receptors and uncover that SARS-CoV-2 binding to heparan sulfates is an important mechanism for neutralization. These results have imperative implications for our understanding of SARS-CoV-2 host cell entry and reveal an important target for novel prophylactic intervention.Competing Interest StatementThe authors have declared no competing interest.

Original language	English
Article number	18.255810
Journal	bioRxiv
DOIs	https://doi.org/10.1101/2020.08.18.255810
Publication status	Published - 2020

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https://doi.org/10.1101/2020.08.18.255810

https://www.biorxiv.org/content/early/2020/08/18/2020.08.18.255810

Cite this

Bermejo-Jambrina, M., Eder, J., Kaptein, T. M., Helgers, L. C., Brouwer, P. J. M., van Hamme, J. L., Vlaar, A. P. J., van Baarle, F. E. H. P., de Bree, G. J., Nijmeijer, B. M., Koostra, N. A., van Gils, M. J., Sanders, R. W., & Geijtenbeek, T. B. H. (2020). SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins. bioRxiv, Article 18.255810. https://doi.org/10.1101/2020.08.18.255810

@article{8a246f38dd9a4539a3faf27385b0ffdf,

title = "SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins",

abstract = "The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and new outbreaks worldwide highlight the need for preventive treatments. Although angiotensin converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2, we identified heparan sulfate proteoglycans expressed by epithelial cells, alveolar macrophages and dendritic cells as co-receptors for SARS-CoV-2. Low molecular weight heparins (LMWH) blocked SARS-CoV-2 infection of epithelial cells and alveolar macrophages, and virus dissemination by dendritic cells. Notably, potent neutralizing antibodies from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, underscoring the importance of heparan sulfate proteoglycans as receptors and uncover that SARS-CoV-2 binding to heparan sulfates is an important mechanism for neutralization. These results have imperative implications for our understanding of SARS-CoV-2 host cell entry and reveal an important target for novel prophylactic intervention.Competing Interest StatementThe authors have declared no competing interest.",

author = "Marta Bermejo-Jambrina and Julia Eder and Kaptein, {Tanja M.} and Helgers, {Leanne C.} and Brouwer, {Philip J.M.} and {van Hamme}, {John L.} and Vlaar, {Alexander P.J.} and {van Baarle}, {Frank E.H.P.} and {de Bree}, {Godelieve J.} and Nijmeijer, {Bernadien M.} and Koostra, {Neeltje A.} and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Geijtenbeek, {Teunis B. H.}",

note = "This article is a preprint and has not been certified by peer review",

year = "2020",

doi = "https://doi.org/10.1101/2020.08.18.255810",

language = "English",

journal = "bioRxiv",

publisher = "Cold Spring Harbor Laboratory Press",

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Bermejo-Jambrina, M, Eder, J , Kaptein, TM , Helgers, LC, Brouwer, PJM, van Hamme, JL , Vlaar, APJ , van Baarle, FEHP , de Bree, GJ, Nijmeijer, BM, Koostra, NA, van Gils, MJ , Sanders, RW & Geijtenbeek, TBH 2020, 'SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins', bioRxiv. https://doi.org/10.1101/2020.08.18.255810

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T1 - SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins

AU - Bermejo-Jambrina, Marta

AU - Eder, Julia

AU - Kaptein, Tanja M.

AU - Helgers, Leanne C.

AU - Brouwer, Philip J.M.

AU - van Hamme, John L.

AU - Vlaar, Alexander P.J.

AU - van Baarle, Frank E.H.P.

AU - de Bree, Godelieve J.

AU - Nijmeijer, Bernadien M.

AU - Koostra, Neeltje A.

AU - van Gils, Marit J.

AU - Sanders, Rogier W.

AU - Geijtenbeek, Teunis B. H.

N1 - This article is a preprint and has not been certified by peer review

PY - 2020

Y1 - 2020

N2 - The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and new outbreaks worldwide highlight the need for preventive treatments. Although angiotensin converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2, we identified heparan sulfate proteoglycans expressed by epithelial cells, alveolar macrophages and dendritic cells as co-receptors for SARS-CoV-2. Low molecular weight heparins (LMWH) blocked SARS-CoV-2 infection of epithelial cells and alveolar macrophages, and virus dissemination by dendritic cells. Notably, potent neutralizing antibodies from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, underscoring the importance of heparan sulfate proteoglycans as receptors and uncover that SARS-CoV-2 binding to heparan sulfates is an important mechanism for neutralization. These results have imperative implications for our understanding of SARS-CoV-2 host cell entry and reveal an important target for novel prophylactic intervention.Competing Interest StatementThe authors have declared no competing interest.

AB - The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and new outbreaks worldwide highlight the need for preventive treatments. Although angiotensin converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2, we identified heparan sulfate proteoglycans expressed by epithelial cells, alveolar macrophages and dendritic cells as co-receptors for SARS-CoV-2. Low molecular weight heparins (LMWH) blocked SARS-CoV-2 infection of epithelial cells and alveolar macrophages, and virus dissemination by dendritic cells. Notably, potent neutralizing antibodies from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, underscoring the importance of heparan sulfate proteoglycans as receptors and uncover that SARS-CoV-2 binding to heparan sulfates is an important mechanism for neutralization. These results have imperative implications for our understanding of SARS-CoV-2 host cell entry and reveal an important target for novel prophylactic intervention.Competing Interest StatementThe authors have declared no competing interest.

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