SARS-CoV-2 Infection, Transmission via Heparan Sulfates, Blocked by Low Molecular Weight Heparins

View ORCID ProfileMarta Bermejo-Jambrina, View ORCID ProfileJulia 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, View ORCID ProfileTeunis B. H. Geijtenbeek

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

PDF: https://www.biorxiv.org/content/10.1101/2020.08.18.255810v1.full.pdf

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 Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2020.08.18.255810v1?rss=1%22