ArticleMolecular systems biology2021
Machine learning identifies molecular regulators and therapeutics for targeting SARS-CoV2-induced cytokine release.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
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- A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Host kinase regulation of Plasmodium vivax dormant and replicating liver stages.PLoS neglected tropical diseases · 2026Article
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts.Cell reports. Medicine · 2025Article
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- Ponatinib Averts αCD40 Antibody Mediated Toxicity by Lowering MAPK38 Expression and Shows Proimmunogenic Effects in a Murine Tumor Model.ACS pharmacology & translational science · 2025Article
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- Significance of Artificial Intelligence in the Study of Virus-Host Cell Interactions.Biomolecules · 2024Review
- Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections.International journal of molecular sciences · 2024Review
- A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.Scientific reports · 2024Article
- A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities.eLife · 2024Article
- Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients.Nature communications · 2024Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases.Viruses · 2023Review
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.bioRxiv : the preprint server for biology · 2023Article
- Circulating Inflammatory Factor Levels in the Early Phase of COVID-19 are Associated with the Progression of Respiratory Failure: A Single-Center Retrospective Study.Journal of inflammation research · 2023Article
- Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference.iScience · 2022Article
- The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although 15-20% of COVID-19 patients experience hyper-inflammation induced by massive cytokine production, cellular triggers of this process and strategies to target them remain poorly understood. Here, we show that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein substantially induces multiple inflammatory molecules in myeloid cells and human PBMCs. Using a combination of phenotypic screening with machine learning-based modeling, we identified and experimentally validated several protein kinases, including JAK1, EPHA7, IRAK1, MAPK12, and MAP3K8, as essential downstream mediators of NTD-induced cytokine production, implicating the role of multiple signaling pathways in cytokine release. Further, we found several FDA-approved drugs, including ponatinib, and cobimetinib as potent inhibitors of the NTD-mediated cytokine release. Treatment with ponatinib outperforms other drugs, including dexamethasone and baricitinib, inhibiting all cytokines in response to the NTD from SARS-CoV-2 and emerging variants. Finally, ponatinib treatment inhibits lipopolysaccharide-mediated cytokine release in myeloid cells in vitro and lung inflammation mouse model. Together, we propose that agents targeting multiple kinases required for SARS-CoV-2-mediated cytokine release, such as ponatinib, may represent an attractive therapeutic option for treating moderate to severe COVID-19.
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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.