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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.
  • Clausen TM; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Infectious Disease, Copenhagen University
  • Sandoval DR; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Spliid CB; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Infectious Disease, Copenhagen University
  • Pihl J; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Infectious Disease, Copenhagen University
  • Perrett HR; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Painter CD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA.
  • Narayanan A; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Majowicz SA; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Kwong EM; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • McVicar RN; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Thacker BE; TEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
  • Glass CA; TEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
  • Yang Z; Copenhagen Center for Glycomics, Department of Molecular and Cellular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Torres JL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Golden GJ; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA.
  • Bartels PL; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Porell RN; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Garretson AF; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Laubach L; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Feldman J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Yin X; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Pu Y; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Hauser BM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Caradonna TM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
  • Kellman BP; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, U
  • Martino C; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
  • Gordts PLSM; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Chanda SK; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Schmidt AG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Godula K; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Leibel SL; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
  • Jose J; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Corbett KD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Carlin AF; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Esko JD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jesko@health.ucsd.edu.
Cell ; 183(4): 1043-1057.e15, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-756808
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptidyl-Dipeptidase A / Spike Glycoprotein, Coronavirus / Betacoronavirus / Heparitin Sulfate Limits: Humans Language: English Journal: Cell Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptidyl-Dipeptidase A / Spike Glycoprotein, Coronavirus / Betacoronavirus / Heparitin Sulfate Limits: Humans Language: English Journal: Cell Year: 2020 Document Type: Article