The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects
Open accessAbstract
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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Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells
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Favalli, E. G., Ingegnoli, F., De Lucia, O., Cincinelli, G., Cimaz, R., & Caporali, R. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102523 · Cited by 454
COVID-19: Drug Targets and Potential Treatments
Gil, C., Ginex, T., Maestro, I., Nozal, V., Barrado-Gil, L., Cuesta-Geijo, M. Á., Urquiza, J., Ramírez, D., Alonso, C., Campillo, N. E., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00606 · Cited by 445
Current pharmacological treatments for COVID‐19: What's next?
Scavone, C., Brusco, S., Bertini, M., Sportiello, L., Rafaniello, C., Zoccoli, A., Berrino, L., Racagni, G., Rossi, F., & Capuano, A. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15072 · Cited by 283
A Comprehensive Review About SARS-CoV-2
Haque, S. M., Ashwaq, O., Sarief, A., & Azad John Mohamed, A. K. (2020) · Future Virology · doi:10.2217/fvl-2020-0124 · Cited by 121
Metadata
- Authors
- Bekerman, E., Neveu, G., Shulla, A., Brannan, J., Pu, S.-Y., Wang, S., Xiao, F., Barouch-Bentov, R., Bakken, R. R., Mateo, R., Govero, J., Nagamine, C. M., Diamond, M. S., De Jonghe, S., Herdewijn, P., Dye, J. M., Randall, G., & Einav, S.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-02-27
- Volume
- 127
- Issue
- 4
- Pages
- 1338-1352
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2590932802
- Cited by
- 226
- References
- 5
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- green
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- Bekerman, E., Neveu, G., Shulla, A., Brannan, J., Pu, S.-Y., Wang, S., Xiao, F., Barouch-Bentov, R., Bakken, R. R., Mateo, R., Govero, J., Nagamine, C. M., Diamond, M. S., De Jonghe, S., Herdewijn, P., Dye, J. M., Randall, G., & Einav, S. (2017). Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects. Journal of Clinical Investigation. https://doi.org/10.1172/jci89857
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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