@article{5fdd3209b8b64a5793de9c026676939e,
title = "SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2",
abstract = "We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2-binding site. Both ACE2 and heparin can bind independently to spike protein in vitro, and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities.",
keywords = "Amino Acid Sequence, Angiotensin-Converting Enzyme 2, Betacoronavirus/isolation & purification, Binding Sites, COVID-19, Cell Line, Coronavirus Infections/pathology, Heparin/chemistry, Heparitin Sulfate/chemistry, Humans, Kidney/metabolism, Lung/metabolism, Molecular Dynamics Simulation, Pandemics, Peptidyl-Dipeptidase A/chemistry, Pneumonia, Viral/pathology, Protein Binding, Protein Domains, Recombinant Proteins/biosynthesis, SARS-CoV-2, Spike Glycoprotein, Coronavirus/chemistry, Virus Internalization",
author = "Clausen, {Thomas Mandel} and Sandoval, {Daniel R} and Spliid, {Charlotte B} and Jessica Pihl and Perrett, {Hailee R} and Painter, {Chelsea D} and Anoop Narayanan and Majowicz, {Sydney A} and Kwong, {Elizabeth M} and McVicar, {Rachael N} and Thacker, {Bryan E} and Glass, {Charles A} and Zhang Yang and Torres, {Jonathan L} and Golden, {Gregory J} and Bartels, {Phillip L} and Porell, {Ryan N} and Garretson, {Aaron F} and Logan Laubach and Jared Feldman and Xin Yin and Yuan Pu and Hauser, {Blake M} and Caradonna, {Timothy M} and Kellman, {Benjamin P} and Cameron Martino and Gordts, {Philip L S M} and Chanda, {Sumit K} and Schmidt, {Aaron G} and Kamil Godula and Leibel, {Sandra L} and Joyce Jose and Corbett, {Kevin D} and Ward, {Andrew B} and Carlin, {Aaron F} and Esko, {Jeffrey D}",
note = "Copyright {\textcopyright} 2020 Elsevier Inc. All rights reserved.",
year = "2020",
month = nov,
day = "12",
doi = "10.1016/j.cell.2020.09.033",
language = "English",
volume = "183",
pages = "1043--1057.e15",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}