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SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2
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; 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.
Affiliation
  • Thomas Mandel Clausen; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Daniel R Sandoval; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Charlotte B Spliid; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Jessica Pihl; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Chelsea D Painter; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Bryan E Thacker; TEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
  • Charles A Glass; TEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
  • Anoop Narayanan; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.
  • Sydney A Majowicz; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.
  • Yang Zhang; Copenhagen Center for Glycomics, Department of Molecular and Cellular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Jonathan L Torres; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gregory J Golden; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ryan Porell; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Aaron F Garretson; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Logan Laubach; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Xin Yin; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute 10901 North Torrey Pines Road,
  • Yuan Pu; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute 10901 North Torrey Pines Road,
  • Blake Hauser; Ragon Institute of MGH, MIT and Harvard, Cambridge MA 02139, USA.
  • Timothy M Caradonna; Ragon Institute of MGH, MIT and Harvard, Cambridge MA 02139, USA.
  • Benjamin P Kellman; Department of Bioengineering, University of California, San Diego.
  • Cameron Martino; Department of Bioengineering, University of California, San Diego.
  • Philip L.S.M. Gordts; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Sandra L Leibel; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
  • Summit K Chanda; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute 10901 North Torrey Pines Road,
  • Aaron G Schmidt; Ragon Institute of MGH, MIT and Harvard, Cambridge MA 02139, USA.
  • Kamil Godula; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
  • Joyce Jose; Department of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.
  • Kevin D Corbett; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Andrew B Ward; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Aaron F Carlin; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Jeffrey D Esko; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Preprint in English | bioRxiv | ID: ppbiorxiv-201616
Journal article
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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 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.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Fulltext
Add to My VHL
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XML
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint