Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation.

Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation. Antiviral Res. 2019 Sep 09;:104598 Authors: Ding X, Krutzik PO, Ghaffari AA, Zhaozhi Y, Miranda D, Cheng G, Ho CM, Nolan GP, Sanchez DJ Abstract As antiviral drug resistance develops and new viruses emerge there is a pressing need to develop strategies to rapidly develop antiviral therapeutics. Here we use phospho-specific flow cytometry to assess perturbations of many different cellular signaling pathways during treatment with drug combinations that are highly effective in blocking Herpes simplex virus type 1 (HSV-1) infection. We discovered two antiviral drug combinations act on distinct signaling pathways, either STAT1 or S6 phosphorylation, to block HSV-1 infection. We focused on upregulation of S6 phosphorylation by HSV-1 infection, and our subsequent finding that ribavirin antagonizes this upregulation of S6 phosphorylation. We go on to show that the S6 kinase inhibitor SL0101 blocks HSV-1 replication in vitro and in an in vivo animal model of HSV-1 infection. Overall, we have used an unbiased analysis of cellular signaling pathways during treatment by antiviral drug combinations to discover a novel antiviral drug target against HSV-1 infection. The outcomes of the approach we present highlight the importance of analyzing how antiviral drugs modulate cellular and pathogen-induced signaling as a method to discover new drug therapy tar...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research