PT  - JOURNAL ARTICLE
AU  - Thomas Mandel Clausen
AU  - Daniel R. Sandoval
AU  - Charlotte B. Spliid
AU  - Jessica Pihl
AU  - Chelsea D. Painter
AU  - Bryan E. Thacker
AU  - Charles A. Glass
AU  - Anoop Narayanan
AU  - Sydney A. Majowicz
AU  - Yang Zhang
AU  - Jonathan L. Torres
AU  - Gregory J. Golden
AU  - Ryan Porell
AU  - Aaron F. Garretson
AU  - Logan Laubach
AU  - Jared Feldman
AU  - Xin Yin
AU  - Yuan Pu
AU  - Blake Hauser
AU  - Timothy M. Caradonna
AU  - Benjamin P. Kellman
AU  - Cameron Martino
AU  - Philip L.S.M. Gordts
AU  - Sandra L. Leibel
AU  - Summit K. Chanda
AU  - Aaron G. Schmidt
AU  - Kamil Godula
AU  - Joyce Jose
AU  - Kevin D. Corbett
AU  - Andrew B. Ward
AU  - Aaron F. Carlin
AU  - Jeffrey D. Esko
TI  - SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2
AID  - 10.1101/2020.07.14.201616
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.14.201616
4099  - http://biorxiv.org/content/early/2020/07/14/2020.07.14.201616.short
4100  - http://biorxiv.org/content/early/2020/07/14/2020.07.14.201616.full
AB  - 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 infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities.Competing Interest StatementJ.D.E. is a co-founder of TEGA Therapeutics. J.D.E. and The Regents of the University of California have licensed a University invention to and have an equity interest in TEGA Therapeutics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. C.A.G and B.E.T are employees of TEGA Therapeutics.