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

Bermejo-Jambrina, M.; Eder, J.; Kaptein, T. M.; Helgers, L. C.; Brouwer, P. J.; van Hamme, J. L.; Vlaar, A. P.; van Baarle, F. E. H. P.; de Bree, G. J.; Nijmeijer, B. M.; Kootstra, N. A.; van Gils, M. J.; Sanders, R. W.; Geijtenbeek, T. B. H.

doi:10.1101/2020.08.18.255810

bioRxiv · 10.1101/2020.08.18.255810

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

Bermejo-Jambrina, M.·Eder, J.·Kaptein, T. M.·Helgers, L. C.·Brouwer, P. J.·van Hamme, J. L.·Vlaar, A. P.·van Baarle, F. E. H. P.·de Bree, G. J.·Nijmeijer, B. M.·Kootstra, N. A.·van Gils, M. J.·Sanders, R. W.·Geijtenbeek, T. B. H.

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Abstract

The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans, and transmitted the virus to ACE2-positive cells. Moreover, human primary nasal cells were infected by SARS-CoV-2 and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.

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Bermejo-Jambrina, M., Eder, J., Kaptein, T. M., Helgers, L. C., Brouwer, P. J., van Hamme, J. L., Vlaar, A. P., van Baarle, F. E. H. P., de Bree, G. J., Nijmeijer, B. M., Kootstra, N. A., van Gils, M. J., Sanders, R. W., Geijtenbeek, T. B. H.. 2020-08-18. SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins. https://doi.org/10.1101/2020.08.18.255810

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