2. Academic Validation
  3. Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation

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

  • Antiviral Res. 2019 Nov:171:104598. doi: 10.1016/j.antiviral.2019.104598.
Xianting Ding 1,  Peter O Krutzik 2,  Amir Ali Ghaffari 3,  Yixiu Zhaozhi 1,  Daniel Miranda Jr 4,  Genhong Cheng 3,  Chih-Ming Ho 5,  Garry P Nolan 2,  David Jesse Sanchez 6
Affiliations

Affiliations

  • 1 Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
  • 2 Microbiology & Immunology - Baxter Laboratory, Stanford University, Palo Alto, CA, USA.
  • 3 Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • 4 Pharmaceutical Sciences Department, Western University of Health Sciences, Pomona, CA, USA.
  • 5 Mechanical and Aerospace Engineering Department, School of Engineering and Applied Science, University of California, Los Angeles, CA, USA.
  • 6 Pharmaceutical Sciences Department, Western University of Health Sciences, Pomona, CA, USA. Electronic address: [email protected].
PMID: 31513822 DOI: 10.1016/j.antiviral.2019.104598
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 targets.

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