Editors' ChoiceVirology

New connections: Kinase inhibitors as antivirals

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Science Signaling  02 Oct 2018:
Vol. 11, Issue 550, eaau2211
DOI: 10.1126/scisignal.aau2211

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  • RE: RE: Kinase inhibitors as antivirals really promising for treatment?

    Kinase inhibitor toxicity is likely influenced by a variety of factors including the role of the target kinase in the cell, the concentration or dose of the inhibitor, and any potential off-target effects. The latter has been a large hurdle to the development of JNKi (1). How kinase inhibitors prevent viral infection is poorly understood and likely differs by kinase target, cell type, and virus.

    The latest research suggests surprising mechanisms of action. For example, although JNK has a known role in cell death (2), studies in IAV (3) and VSV (4) suggest that SP600125, an ATP-competitive JNK inhibitor of poor specificity, prevents viral uncoating by altering the glycosylation of viral structural proteins. Similarly, GRK2 is best characterized in GPCR signaling. Further research on how kinase inhibitors work during infection may uncover equally surprising cell biology mechanisms. It is true that carefully understanding the effects of kinase inhibitors on the immune system is critical for their application. In the case of JNKi, it is possible that when used at the correct dose the inhibitory effects of JNK1 inhibition may be offset by the activation of JNK2 in antiviral T cells (5). However, the highlighted Science Signaling article suggests that the effects of SP600125 in vivo are a consequence of JNKi therapy dampening viral-induced immunopathology.

    References

    1. A. Messoussi, C. Feneyrolles, A. Bros, A. Deroide, B. Daydé-Cazals, G. Che...

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    Competing Interests: None declared.
  • RE: Kinase inhibitors as antivirals really promising for treatment?

    Most of the kinase inhibitors are cytotoxic; the reduction in the disease may due to killing of the cell which results in elimination of the virus. Also, would these kinase inhibitors have higher effect on cell growth of immune cells, which results in further infection?
    Please clear my thoughts on kinase inhibitors as antivirals so that I use this approach for my research

    Competing Interests: None declared.

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