Infection and transmission of SARS-CoV-2 depends on heparan sulfate proteoglycans

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

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.