ArticleAntiviral research2020
BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.
Article in Antiviral research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Meta-analysis of cellular phosphoproteome datasets exploring phospho-signaling associated with the RNA-binding protein RAVER1.Scientific reports · 2026Pooled it
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Numb-Associated Kinases-Mediated AP2M1 Activation Facilitates Porcine Reproductive and Respiratory Syndrome Virus Entry.Transboundary and emerging diseases · 2026Article
- Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.European journal of medicinal chemistry · 2025Article
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Curcumin prevents dexamethasone-induced activation of the pseudorabies virus in rat pheochromocytoma cells through the miR-155-5p-Aak1-Numb/Notch2 signalling axis.Veterinary research · 2025Article
- Virus infection and vesicle trafficking.Frontiers in immunology · 2025Review
- ELM-the Eukaryotic Linear Motif resource-2024 update.Nucleic acids research · 2024Article
- Preparing for the next viral threat with broad-spectrum antivirals.The Journal of clinical investigation · 2023Review
- Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies.Antiviral research · 2022Article
- The cargo adapter protein CLINT1 is phosphorylated by the Numb-associated kinase BIKE and mediates dengue virus infection.The Journal of biological chemistry · 2022Article
- Kinase Inhibitors as Underexplored Antiviral Agents.Journal of medicinal chemistry · 2022Review
- Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents.Frontiers in chemistry · 2022Article
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Global health is threatened by emerging viruses, many of which lack approved therapies and effective vaccines, including dengue, Ebola, and Venezuelan equine encephalitis. We previously reported that AAK1 and GAK, two of the four members of the understudied Numb-associated kinases (NAK) family, control intracellular trafficking of RNA viruses. Nevertheless, the role of BIKE and STK16 in viral infection remained unknown. Here, we reveal a requirement for BIKE, but not STK-16, in dengue virus (DENV) infection. BIKE mediates both early (postinternalization) and late (assembly/egress) stages in the DENV life cycle, and this effect is mediated in part by phosphorylation of a threonine 156 (T156) residue in the μ subunit of the adaptor protein (AP) 2 complex. Pharmacological compounds with potent anti-BIKE activity, including the investigational anticancer drug 5Z-7-oxozeaenol and more selective inhibitors, suppress DENV infection both in vitro and ex vivo. BIKE overexpression reverses the antiviral activity, validating that the mechanism of antiviral action is, at least in part, mediated by BIKE. Lastly, 5Z-7-oxozeaenol exhibits antiviral activity against viruses from three unrelated RNA viral families with a high genetic barrier to resistance. These findings reveal regulation of poorly understood stages of the DENV life cycle via BIKE signaling and establish a proof-of-principle that pharmacological inhibition of BIKE can be potentially used as a broad-spectrum strategy against acute emerging viral infections.
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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 Socratic graph.