ArticleNature communications2024
De novo design of miniprotein antagonists of cytokine storm inducers.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed.
- Article
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- Review
- Progress in Designing Cytokine Antagonist Antibodies for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Targeting the astrocyte-microglia EFEMP1-GALNT10 axis: a spatially programmable therapeutic strategy for hippocampal vulnerability in Alzheimer's disease.Journal of translational medicine · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- Design of miniprotein inhibitors targeting complement C9 to block membrane attack complex assembly.Nature communications · 2026Article
- De novo protein design: a transformative frontier in clinical protein applications.Journal of translational medicine · 2026Review
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Inter-organ crosstalk in systemic inflammation: a narrative review of molecular mechanisms and pharmacological modulation in the muscle-adipose-liver axis.Frontiers in pharmacology · 2026Review
- Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists.bioRxiv : the preprint server for biology · 2025Article
- Potential Transmembrane Proteins-transporters of Chelidonic Acid for its Intracellular Uptake: In Silico Simulation.Pharmaceutical research · 2025Article
- The Role of AI-Driven De Novo Protein Design in the Exploration of the Protein Functional Universe.Biology · 2025Review
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Article
- Microbial production of chondroitin sulfate and its derivatives.Science China. Life sciences · 2025Article
- AI-assisted design of ligands for lipocalin-2.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Cytokine release syndrome (CRS), commonly known as cytokine storm, is an acute systemic inflammatory response that is a significant global health threat. Interleukin-6 (IL-6) and interleukin-1 (IL-1) are key pro-inflammatory cytokines involved in CRS and are hence critical therapeutic targets. Current antagonists, such as tocilizumab and anakinra, target IL-6R/IL-1R but have limitations due to their long half-life and systemic anti-inflammatory effects, making them less suitable for acute or localized treatments. Here we present the de novo design of small protein antagonists that prevent IL-1 and IL-6 from interacting with their receptors to activate signaling. The designed proteins bind to the IL-6R, GP130 (an IL-6 co-receptor), and IL-1R1 receptor subunits with binding affinities in the picomolar to low-nanomolar range. X-ray crystallography studies reveal that the structures of these antagonists closely match their computational design models. In a human cardiac organoid disease model, the IL-1R antagonists demonstrated protective effects against inflammation and cardiac damage induced by IL-1β. These minibinders show promise for administration via subcutaneous injection or intranasal/inhaled routes to mitigate acute cytokine storm effects.
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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.