ArticleCell2020
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.
2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 795 papers.
0numbers the graph read from it
0cells of the map it votes in
795citing papers in PubMed
22.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NCT05204550 phase2 / phase3completednot on this mapstarted 2023, after this paper: background citation
A Randomised, Placebo-controlled Trial to Investigate the Efficacy of Intranasal Heparin Treatment to Reduce Transmission of SARS-CoV-2 Infection and COVID 19 Disease Among Household Contacts of SARS-CoV-2+ Adults and Children
A Randomized, Placebo-controlled, Double-blind, Monocenter, Phase II Trial to Assess the Efficacy of Calcium Dobesilate (CaD) vs. Placebo on SARS-CoV-2 Viral Load Amongst Outpatients With COVID-19.
Who cites it
795 citing papers in PubMed, 1,182 citations in OpenAlex.
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- Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.Scientific reports · 2024Trial
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- Identification of Prohibitin (PHB) as an Entry Factor of Highly Pathogenic Coronaviruses Using Metabolic Glycoengineering and Photo-Crosslinking Techniques.Emerging microbes & infections · 2026Article
- The essential role of heparan sulfate in the entry of PDCoV and other porcine coronaviruses.Virulence · 2026Article
- Endothelial Exostosin-1 Is Needed for Glycocalyx Integrity and Inflammatory Resolution in Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain.Science advances · 2026Article
- Mucins and Respiratory Virus Infection.Annual review of virology · 2026Review
- Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.eLife · 2026Article
- Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection.Basic & clinical pharmacology & toxicology · 2026Review
- Clinical dose of enoxaparin enhances oncolytic virus M1 infection and antitumor efficacy in human bladder cancer.iScience · 2026Article
- Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.Nature communications · 2026Article
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- Controlled Triazine-Based Covalent Functionalization of Black Phosphorus for Degradable Hybrid Materials.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- CCHFV GP38 and GP85 interact with cell-surface glycosaminoglycans.Npj viruses · 2026Article
- Antiviral Activity of Dendritic Heparan Sulfate Mimetics against Respiratory Syncytial Virus and Herpes Simplex Virus‑1.ACS omega · 2026Article
- Challenges in developing broad-spectrum viral attachment inhibitors targeting heparan sulfates and sialic acids.Journal of virology · 2026Review
- Review
- Interactys-AI: Toward AI-Driven Structural Mapping of Virus-Host Interfaces for Antiviral Repurposing and Pandemic Preparedness.Biomolecules · 2026Review
- Heparan sulfate as an attachment factor for ASFV is restricted by host HB-EGF.Cellular and molecular life sciences : CMLS · 2026Article
735 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 8 institutions in 2 countries.
Thomas Mandel ClausenDepartment 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 Hospital, 2200 Copenhagen, Denmark. Electronic address: tmandelclausen@health.ucsd.edu.
Daniel R SandovalDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Charlotte B SpliidDepartment 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 Hospital, 2200 Copenhagen, Denmark.
Jessica PihlDepartment 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 Hospital, 2200 Copenhagen, Denmark.
Hailee R PerrettDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chelsea D PainterDepartment 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.
Anoop NarayananDepartment of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Sydney A MajowiczDepartment of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Elizabeth M KwongSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Rachael N McVicarSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Bryan E ThackerTEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
Charles A GlassTEGA Therapeutics, Inc., 3550 General Atomics Court, G02-102, San Diego, CA 92121, USA.
Zhang YangCopenhagen Center for Glycomics, Department of Molecular and Cellular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gregory J GoldenDepartment 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.
Phillip L BartelsDepartment 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.
Ryan N PorellDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Aaron F GarretsonDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Logan LaubachDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Jared FeldmanRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Xin YinImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yuan PuImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Blake M HauserRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Timothy M CaradonnaRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Benjamin P KellmanDepartment 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, USA.
Cameron MartinoDepartment 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.
Philip L S M GordtsDepartment 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.
Sumit K ChandaImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Aaron G SchmidtRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Kamil GodulaDepartment 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.
Sandra L LeibelDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
Joyce JoseDepartment of Biochemistry and Molecular Biology, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Kevin D CorbettDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aaron F CarlinDepartment of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Jeffrey D EskoDepartment 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.
University of California San Diego · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of Copenhagen · DKPennsylvania State University · USRagon Institute of MGH, MIT and Harvard · USScripps Research Institute · USGeneral Atomics (United States) · USHarvard University · US
Funding
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MProtein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MARTH, JAMEY · 2016 to 2025
$26.2MSiglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHOUDHURY, BISWA · 2011 to 2017
$18.0MMOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6MMOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3MUCSD Biomedical Scientist Career Development Program in GlycoscienceK12HL141956 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, GODULA, KAMIL · 2018 to 2022
$5.3MEXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Amit Majithia · 1986 to 2026
$4.6MEpitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2MIn vivo glycan engineering at the cell-matrix interface to control stem cell fateDP2HD087954 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GODULA, KAMIL · 2015 to 2015
$2.3MExpanding the CRISPR/Cas toolbox for RNA modulationR01GM128464 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CORBETT, KEVIN DANIEL · 2018 to 2021
$863kNHLBI NIH HHS K12 HL141956NHLBI NIH HHS P01 HL107150NHLBI NIH HHS P01 HL131474NIAID NIH HHS R01 AI146779NIAID NIH HHS T32 AI007245NIAID NIH HHS U19 AI135972NICHD NIH HHS DP2 HD087954NIDDK NIH HHS T32 DK007044NIGMS NIH HHS R01 GM128464NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
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.
Indexed as
Amino Acid SequenceAngiotensin-Converting Enzyme 2BetacoronavirusBinding SitesCell LineCoronavirus InfectionsCOVID-19Heparan SulfateHeparinHumansKidneyLungMolecular Dynamics SimulationPandemicsPeptidyl-Dipeptidase APneumonia, ViralACE2 protein, humanAngiotensin-Converting Enzyme 2Heparan SulfateHeparinPeptidyl-Dipeptidase ARecombinant ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2coronavirusCOVID-19heparan sulfateheparan sulfate-binding proteinsheparinlung epithelial cellspseudotyped virusSARS-CoV-2spike proteins
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Registered trials
NCT05204550ClinicalTrials.gov
NCT05305508ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.