ArticleScientific reports2022
Mitoxantrone modulates a heparan sulfate-spike complex to inhibit SARS-CoV-2 infection.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- The essential role of heparan sulfate in the entry of PDCoV and other porcine coronaviruses.Virulence · 2026Article
- MD Simulation of Vector-Receptor Pharmacologic Pairs for Tumor-Specific Drug Delivery: Transfer of Boron Atoms by RGD Peptide to αvβ3 Integrin Receptor.Current issues in molecular biology · 2026Article
- Deep Learning-Guided Discovery of Dual Inhibitors of SARS-CoV-2 Entry and 3CL Protease.Molecules (Basel, Switzerland) · 2026Article
- Heparin-Binding Proteins in the Nanoparticle Corona Enhance Cellular Uptake through Glycocalyx Interactions.ACS nano · 2025Article
- Mechanism-informed identification of FDA-approved topoisomerase inhibitors disrupting SARS-CoV-2 nucleocapsid-RNA interactions.BMC chemistry · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry.Frontiers in pharmacology · 2025Article
- Glycocalyx Interactions Modulate the Cellular Uptake of Albumin-Coated Nanoparticles.ACS applied bio materials · 2024Article
- Therapeutic development targeting host heparan sulfate proteoglycan in SARS-CoV-2 infection.Frontiers in medicine · 2024Review
- Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation.Nature communications · 2023Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- In Vitro and In Vivo Therapeutic Potential of 6,6'-Dihydroxythiobinupharidine (DTBN) fromInternational journal of molecular sciences · 2023Article
- Heparan sulfate promotes ACE2 super-cluster assembly to enhance SARS-CoV-2-associated syncytium formation.Research square · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA-approved topoisomerase inhibitor, targets a heparan sulfate-spike complex to compromise the fusogenic function of spike in viral entry. As a single agent, Mitoxantrone inhibits the infection of an authentic SARS-CoV-2 strain in a cell-based model and in human lung EpiAirway 3D tissues. Gene expression profiling supports the plasma membrane as a major target of Mitoxantrone but also underscores an undesired activity targeting nucleosome dynamics. We propose that Mitoxantrone analogs bearing similar heparan sulfate-binding activities but with reduced affinity for DNA topoisomerases may offer an alternative therapy to overcome breakthrough infections in the post-vaccine era.
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Registered trials
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