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SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2

biorxiv. 2020-07-01; 
Thomas Mandel Clausen, Daniel R Sandoval, Charlotte B Spliid, Jessica Pihl, Chelsea D Painter, Bryan E Thacker, Charles A Glass, Anoop Narayanan, Sydney A Majowicz, Yang Zhang, Jonathan L Torres, Gregory J Golden, Ryan Porell, Aaron F Garretson, Logan Laubach, Jared Feldman, Xin Yin, Yuan Pu, Blake Hauser, Timothy M Caradonna, Benjamin P Kellman, Cameron Martino, Philip L S M Gordts, Sandra L Leibel, Summit K Chanda, Aaron G Schmidt, Kamil Godula, Joyce Jose, Kevin D Corbett, Andrew B Ward, Aaron F Carlin, Jeffrey D Esko
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Abstract

We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and inf... More

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