ArticleAntiviral research2022
Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies.
Article in Antiviral research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration.Nature communications · 2026Article
- Genetic variations in AAK1 and ADAM17 associated with circulatory cytokines changes influence COVID-19 susceptibility and severity.Human genomics · 2026Article
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti-Tumor Activity Against Ewing Sarcoma.Archiv der Pharmazie · 2026Article
- Numb-Associated Kinases-Mediated AP2M1 Activation Facilitates Porcine Reproductive and Respiratory Syndrome Virus Entry.Transboundary and emerging diseases · 2026Article
- Phospho-activated non-muscle myosin IIA heavy chain supports different mechanisms of virus uptake.Journal of virology · 2025Article
- Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.European journal of medicinal chemistry · 2025Article
- PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.Nature communications · 2025Article
- 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
- Pyrimidine: A Privileged Scaffold for the Development of Anticancer Agents as Protein Kinase Inhibitors (Recent Update).Current pharmaceutical design · 2025Review
- Numb-associated kinases regulate sandfly-borne Toscana virus entry.Emerging microbes & infections · 2024Article
- Article
- Development of a novel AAK1 inhibitor via Kinobeads-based screening.Scientific reports · 2024Article
- ELM-the Eukaryotic Linear Motif resource-2024 update.Nucleic acids research · 2024Article
- Antimicrobial Potential of Natural Compounds of Zingiberaceae Plants and their Synthetic Analogues: A Scoping Review ofCurrent topics in medicinal chemistry · 2024Article
- Review
- Preparing for the next viral threat with broad-spectrum antivirals.The Journal of clinical investigation · 2023Review
- Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.MedComm · 2023Review
- From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.International journal of molecular sciences · 2023Review
- Current thoughts on cellular functions of numb-associated kinases.Molecular biology reports · 2023Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AAK1, BIKE, GAK, and STK16, the fourth member of the NAK family, suppressed SARS-CoV-2 infection in human lung epithelial cells. Both known and novel small molecules with potent AAK1/BIKE, GAK or STK16 activity suppressed SARS-CoV-2 infection. Moreover, combination treatment with the approved anti-cancer drugs, sunitinib and erlotinib, with potent anti-AAK1/BIKE and GAK activity, respectively, demonstrated synergistic effect against SARS-CoV-2 infection in vitro. Time-of-addition experiments revealed that pharmacological inhibition of AAK1 and BIKE suppressed viral entry as well as late stages of the SARS-CoV-2 life cycle. Lastly, suppression of NAKs expression by siRNAs inhibited entry of both wild type and SARS-CoV-2 pseudovirus. These findings provide insight into the roles of NAKs in SARS-CoV-2 infection and establish a proof-of-principle that pharmacological inhibition of NAKs can be potentially used as a host-targeted approach to treat SARS-CoV-2 with potential implications to other coronaviruses.
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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 Socratic graph.