ArticleThe Journal of clinical investigation2017
Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.
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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
137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 233 citations in OpenAlex.
- A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials.Life sciences · 2020Pooled it
- Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.Current neuropharmacology · 2019Pooled it
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Sulfonyl Anthranilic Acid Analogues Display Pan-Serotype Anti-Dengue Activity by Downregulating the Expression of Ribosomal Proteins Encoded by 5'-Terminal Oligopyrimidine Motif-Containing mRNA.Journal of medicinal chemistry · 2026Article
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Discovery and optimization of AAK1 inhibitors based on 1H-indazole scaffold for the potential treatment of SARS-CoV-2 infection.Molecular diversity · 2026Article
- Multifaceted Small Molecules as Enzyme Modulators: Cases of Drug Discovery/Repurposing Illustrating Nature's Pragmatism.BioMed research international · 2026Review
- Numb-Associated Kinases-Mediated AP2M1 Activation Facilitates Porcine Reproductive and Respiratory Syndrome Virus Entry.Transboundary and emerging diseases · 2026Article
- Discovery of antivirally active inhibitors of adaptor protein-2 associated kinase 1 based on various bicyclic heteroaromatic scaffolds derived from a 7-azaindole analogue.European journal of medicinal chemistry · 2025Article
- Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.European journal of medicinal chemistry · 2025Article
- Chemoprevention of hepatocellular carcinoma.Hepatology communications · 2025Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Host centric drug repurposing for viral diseases.PLoS computational biology · 2025Article
- Numb-associated kinases regulate sandfly-borne Toscana virus entry.Emerging microbes & infections · 2024Article
- Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors.Journal of medicinal chemistry · 2024Article
- Baricitinib and Pulse Steroids Combination Treatment in Hyperinflammatory COVID-19: A Rheumatological Approach in the Intensive Care Unit.International journal of molecular sciences · 2024Article
- The endoplasmic reticulum (ER): a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions.Npj viruses · 2024Review
- Development of a novel AAK1 inhibitor via Kinobeads-based screening.Scientific reports · 2024Article
- Recent advances in the treatment of Ebola disease: A brief overview.PLoS pathogens · 2024Review
- Synthesis of a 3,7-Disubstituted Isothiazolo[4,3-Molecules (Basel, Switzerland) · 2024Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses.
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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.