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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. / Clausen, Thomas Mandel; Sandoval, Daniel R.; Spliid, Charlotte B.; Pihl, Jessica; Perrett, Hailee R.; Painter, Chelsea D.; Narayanan, Anoop; Majowicz, Sydney A.; Kwong, Elizabeth M.; McVicar, Rachael N.; Thacker, Bryan E.; Glass, Charles A.; Yang, Zhang; Torres, Jonathan L.; Golden, Gregory J.; Bartels, Phillip L.; Porell, Ryan N.; Garretson, Aaron F.; Laubach, Logan; Feldman, Jared; Yin, Xin; Pu, Yuan; Hauser, Blake M.; Caradonna, Timothy M.; Kellman, Benjamin P.; Martino, Cameron; Gordts, Philip L.S.M.; Chanda, Sumit K.; Schmidt, Aaron G.; Godula, Kamil; Leibel, Sandra L.; Jose, Joyce; Corbett, Kevin D.; Ward, Andrew B.; Carlin, Aaron F.; Esko, Jeffrey D.

I: Cell, Bind 183, Nr. 4, 2020, s. 1043-1057.e15.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Clausen, TM, Sandoval, DR, Spliid, CB, Pihl, J, Perrett, HR, Painter, CD, Narayanan, A, Majowicz, SA, Kwong, EM, McVicar, RN, Thacker, BE, Glass, CA, Yang, Z, Torres, JL, Golden, GJ, Bartels, PL, Porell, RN, Garretson, AF, Laubach, L, Feldman, J, Yin, X, Pu, Y, Hauser, BM, Caradonna, TM, Kellman, BP, Martino, C, Gordts, PLSM, Chanda, SK, Schmidt, AG, Godula, K, Leibel, SL, Jose, J, Corbett, KD, Ward, AB, Carlin, AF & Esko, JD 2020, 'SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2', Cell, bind 183, nr. 4, s. 1043-1057.e15. https://doi.org/10.1016/j.cell.2020.09.033

APA

Clausen, T. M., Sandoval, D. R., Spliid, C. B., Pihl, J., Perrett, H. R., Painter, C. D., Narayanan, A., Majowicz, S. A., Kwong, E. M., McVicar, R. N., Thacker, B. E., Glass, C. A., Yang, Z., Torres, J. L., Golden, G. J., Bartels, P. L., Porell, R. N., Garretson, A. F., Laubach, L., ... Esko, J. D. (2020). SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell, 183(4), 1043-1057.e15. https://doi.org/10.1016/j.cell.2020.09.033

Vancouver

Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD o.a. SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell. 2020;183(4):1043-1057.e15. https://doi.org/10.1016/j.cell.2020.09.033

Author

Clausen, Thomas Mandel ; Sandoval, Daniel R. ; Spliid, Charlotte B. ; Pihl, Jessica ; Perrett, Hailee R. ; Painter, Chelsea D. ; Narayanan, Anoop ; Majowicz, Sydney A. ; Kwong, Elizabeth M. ; McVicar, Rachael N. ; Thacker, Bryan E. ; Glass, Charles A. ; Yang, Zhang ; Torres, Jonathan L. ; Golden, Gregory J. ; Bartels, Phillip L. ; Porell, Ryan N. ; Garretson, Aaron F. ; Laubach, Logan ; Feldman, Jared ; Yin, Xin ; Pu, Yuan ; Hauser, Blake M. ; Caradonna, Timothy M. ; Kellman, Benjamin P. ; Martino, Cameron ; Gordts, Philip L.S.M. ; Chanda, Sumit K. ; Schmidt, Aaron G. ; Godula, Kamil ; Leibel, Sandra L. ; Jose, Joyce ; Corbett, Kevin D. ; Ward, Andrew B. ; Carlin, Aaron F. ; Esko, Jeffrey D. / SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. I: Cell. 2020 ; Bind 183, Nr. 4. s. 1043-1057.e15.

Bibtex

@article{a1156f3eff8c4521b177debdc66404a2,

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 = "coronavirus, COVID-19, heparan sulfate, heparan sulfate-binding proteins, heparin, lung epithelial cells, pseudotyped virus, SARS-CoV-2, spike proteins",

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.}",

year = "2020",

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",

}

RIS

TY - JOUR

T1 - SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2

AU - Clausen, Thomas Mandel

AU - Sandoval, Daniel R.

AU - Spliid, Charlotte B.

AU - Pihl, Jessica

AU - Perrett, Hailee R.

AU - Painter, Chelsea D.

AU - Narayanan, Anoop

AU - Majowicz, Sydney A.

AU - Kwong, Elizabeth M.

AU - McVicar, Rachael N.

AU - Thacker, Bryan E.

AU - Glass, Charles A.

AU - Yang, Zhang

AU - Torres, Jonathan L.

AU - Golden, Gregory J.

AU - Bartels, Phillip L.

AU - Porell, Ryan N.

AU - Garretson, Aaron F.

AU - Laubach, Logan

AU - Feldman, Jared

AU - Yin, Xin

AU - Pu, Yuan

AU - Hauser, Blake M.

AU - Caradonna, Timothy M.

AU - Kellman, Benjamin P.

AU - Martino, Cameron

AU - Gordts, Philip L.S.M.

AU - Chanda, Sumit K.

AU - Schmidt, Aaron G.

AU - Godula, Kamil

AU - Leibel, Sandra L.

AU - Jose, Joyce

AU - Corbett, Kevin D.

AU - Ward, Andrew B.

AU - Carlin, Aaron F.

AU - Esko, Jeffrey D.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - coronavirus

KW - COVID-19

KW - heparan sulfate

KW - heparan sulfate-binding proteins

KW - heparin

KW - lung epithelial cells

KW - pseudotyped virus

KW - SARS-CoV-2

KW - spike proteins

U2 - 10.1016/j.cell.2020.09.033

DO - 10.1016/j.cell.2020.09.033

M3 - Journal article

C2 - 32970989

AN - SCOPUS:85091607317

VL - 183

SP - 1043-1057.e15

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -

ID: 249770665