Nucleoside analogue-based drugs control herpes simplex virus type 1 (HSV-1) infection of the eye, but are limited by potential drug resistance and adverse effects. Jaishankar and colleagues report that the small-molecule TANK-binding kinase 1 (TBK1) inhibitor, BX795, suppresses HSV-1 infection in transformed and primary human cells, organ cultures of human and pig corneas, and in a mouse model of ocular HSV infection. This antiviral activity was mediated by an off-target effect, comprised of inhibition of AKT phosphorylation in infected cells, leading to blockade of viral protein synthesis.
References
Jaishankar, D. et al. An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye. Sci. Transl Med. 10, eaan5861 (2018)10.1126/scitranslmed.aan5861
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Crunkhorn, S. Topical therapy for ocular herpes. Nat Rev Drug Discov 17, 242 (2018). https://doi.org/10.1038/nrd.2018.47
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DOI: https://doi.org/10.1038/nrd.2018.47