ArticleACS central science2022
Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction.
Article in ACS central science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The trial behind it
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Who cites it
64 citing papers in PubMed, 106 citations in OpenAlex.
- Targeting virus-glycan recognition in influenza viruses and coronaviruses: from the molecular principles to glycomimetic antivirals strategies.RSC chemical biology · 2026Review
- Virus-Mediated Self-Assembly of Functional Cyclodextrins for Antiviral Inhibition.Angewandte Chemie (International ed. in English) · 2026Article
- Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.eLife · 2026Article
- Autonomous intranasal delivery systems for central nervous system therapeutics.Experimental & molecular medicine · 2026Review
- Antiviral Activity of Dendritic Heparan Sulfate Mimetics against Respiratory Syncytial Virus and Herpes Simplex Virus‑1.ACS omega · 2026Article
- Synthesis of Sulfated Glycomimetics with Micromolar Affinity for Midkine.The Journal of organic chemistry · 2026Article
- K5 polysaccharides inhibit SARS-CoV-2 infection by preventing spike-proteolytic priming.Npj viruses · 2026Article
- From Native Glycosaminoglycans to Mimetics: Design, Mechanisms, and Biomedical Applications.Biomolecules · 2025Review
- D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Controlling the Sulfation Density of Glycosaminoglycan Glycopolymer Mimetics Enables High Antiviral Activity against SARS-CoV-2 and Reduces Anticoagulant Activity.Biomacromolecules · 2025Article
- Low-Background His-Tag-Targeting Probes for Turn-On Fluorescence Detection of Cell Surface Proteins and Their Binding Interactions.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Broad-Spectrum Antiviral Styrene Maleic-Acid Copolymer Lipid Particle Nanodiscs for pH-Responsive Irreversible Virus Inactivation.Biomacromolecules · 2025Article
- Exploring co-infection dynamics and immune response interactions between COVID-19 and Monkeypox: implications for disease severity, viral transmission, and vaccine efficacy.Virology journal · 2025Review
- Identification of an Unnatural Sulfated Monosaccharide as a High-Affinity Ligand for Pan-Variant Targeting of SARS-CoV-2 Spike Glycoprotein.ACS chemical biology · 2025Article
- Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity.Communications biology · 2025Article
- Synthesis of Low-Molecular-Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS-CoV-2 Infection.Angewandte Chemie (International ed. in English) · 2025Article
- A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Establishment of a Yeast Two-Hybrid-Based High-Throughput Screening Model for Selection of SARS-CoV-2 Spike-ACE2 Interaction Inhibitors.International journal of molecular sciences · 2025Article
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
Identifiers
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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.