Sunday, March 5, 2017

Kinase Inhibitors Impair Intracellular Viral Trafficking

Shirit Einav’s lab at Stanford is exploring cell-targeted therapies that work against emerging viral infections. Cell targets can often have broader effects pathogens and they are also less likely to fail due to emergent resistance than traditional virus targeting therapies.

To this end, Shirit’s lab just released a paper in the Journal of Clinical Investigation that shows that two anticancer drugs show broad-spectrum effects against several types of viruses. Sunitinib and erlotinib inhibit AAK1 and GAK activity. Einav’s lab had previously revealed that these two kinases have an important role in intracellular viral formation and release in Hepatitis C virus, as well as several other viruses. When these drugs were explored as options to inhibit kinase activity, the Einav lab was hopeful but unsure as to whether or not they would significantly alter viral loads. Amazingly, in both Hepatitis C and then Dengue, these drugs worked both in vitro and in vivo. This is not wholly surprising because both viruses are members of the flavivirus family, but the news was heartening as it was still more broadly applicable than traditional “one bug one drug” approaches.

Encouraged, the lab has tried the drugs alone and in combination with several other flaviviruses (WNV and Zika), which have showed promise in vitro. To explore the drugs’ potential against other viral target, the lab also studied the effects against Ebola virus, Junin Virus, Chikungunya, and Respiratory Syncytial Virus. All other viral targets also showed preliminary promising responses to the anticancer therapy. Eolba was studied additionally in vivo, and the mice involved showed about a 30-50% reduction in viral loads.

The Einav lab has uncovered a promising new viral therapy, and has also discovered what seems to be a widely used viral mechanism for replication and egress. Let’s hope that further studies lead to more promising results!


Elisa Hofmeister  ‘18


Citation:


Bekerman, E., Neveu, G., Shulla, A., Brannan, J., Pu, S., Wang, S., . . . Einav, S. (2017). Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects. Journal of Clinical Investigation. doi:10.1172/jci89857

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