ArticleNature communications2023
Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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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.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- The essential role of heparan sulfate in the entry of PDCoV and other porcine coronaviruses.Virulence · 2026Article
- Switching Spike Plasticity Shapes ACE2 Engagement Across SARS-CoV-2 Variants.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.eLife · 2026Article
- Article
- Article
- Challenges in developing broad-spectrum viral attachment inhibitors targeting heparan sulfates and sialic acids.Journal of virology · 2026Review
- Disruption of spike protein N-glycosylation induces its endoplasmic reticulum retention and attenuates SARS-CoV-2 infectivity.Journal of virology · 2026Article
- Deep Learning-Guided Discovery of Dual Inhibitors of SARS-CoV-2 Entry and 3CL Protease.Molecules (Basel, Switzerland) · 2026Article
- Insights into the self-assembly and interaction of sars-cov-2 fusion peptides with biomimetic plasma membranes.Nature communications · 2025Article
- Mechanism-informed identification of FDA-approved topoisomerase inhibitors disrupting SARS-CoV-2 nucleocapsid-RNA interactions.BMC chemistry · 2025Article
- Influence of COVID-19 on endocrine and metabolic profiles in women with pathological ovarian aging.Journal of ovarian research · 2025Observational
- Functional diversity in GII.4 norovirus entry: HBGA binding and capsid clustering dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Beyond the Secretory Pathway: New Insights Into Protein Release.Traffic (Copenhagen, Denmark) · 2025Review
- Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity.Communications biology · 2025Article
- FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry.Frontiers in pharmacology · 2025Article
- Review
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties.Journal of translational medicine · 2024Article
- The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein.Viruses · 2024Article
- Therapeutic development targeting host heparan sulfate proteoglycan in SARS-CoV-2 infection.Frontiers in medicine · 2024Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering, forming synapse-like cell-cell contacts that facilitate fusion pore formation between ACE2-expresing and spike-transfected human cells. Chemical or genetic inhibition of HS mitigates ACE2 clustering, and thus, syncytium formation, whereas in a cell-free system comprising purified HS and lipid-anchored ACE2, HS stimulates ACE2 clustering directly in the presence of spike. Furthermore, HS-stimulated syncytium formation and receptor clustering require a conserved ACE2 linker distal from the spike-binding site. Importantly, the cell fusion-boosting function of HS can be targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice. Thus, HS, as a host factor exploited by SARS-CoV-2 to facilitate receptor clustering and a stimulator of infection-associated syncytium formation, may be a promising therapeutic target for severe COVID.
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Registered trials
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.