Evidence map›Paper›PMID 31513822›Full record

ArticleAntiviral research2019

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

Xianting Ding, Peter O Krutzik, Amir Ali Ghaffari, Yixiu Zhaozhi, Daniel Miranda, Genhong Cheng, Chih-Ming Ho, Garry P Nolan, David Jesse Sanchez

Open access · bronzeAbstract read
In one paragraph

Article in Antiviral research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Therapeutic targeting of p90 ribosomal S6 kinase.Frontiers in cell and developmental biology · 2023
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Xianting DingInstitute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
Peter O KrutzikMicrobiology & Immunology - Baxter Laboratory, Stanford University, Palo Alto, CA, USA.
Amir Ali GhaffariDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
Yixiu ZhaozhiInstitute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
Daniel MirandaPharmaceutical Sciences Department, Western University of Health Sciences, Pomona, CA, USA.
Genhong ChengDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
Chih-Ming HoMechanical and Aerospace Engineering Department, School of Engineering and Applied Science, University of California, Los Angeles, CA, USA.
Garry P NolanMicrobiology & Immunology - Baxter Laboratory, Stanford University, Palo Alto, CA, USA.
David Jesse SanchezPharmaceutical Sciences Department, Western University of Health Sciences, Pomona, CA, USA. Electronic address: sanchezd@westernu.edu.
University of California, Los Angeles · USStanford University · USWestern University of Health Sciences · USShanghai Jiao Tong University · CNState Key Laboratory of Oncogene and Related Genes · CN

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
The Center for Systemic Control of Cyto-NetworksPN2EY018228 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HO, CHIH-MING · 2006 to 2010
$8.2M
Manipulation of Type I Interferon by HIV InfectionR15AI138847 · NIAID · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI SANCHEZ, DAVID JESSE · 2018 to 2018
$423k
NEI NIH HHS PN2 EY018228NIAID NIH HHS R15 AI138847NIAID NIH HHS U19 AI057229
6 · The paper itself

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.

Indexed as

AnimalsAntiviral AgentsBiomarkersCell LineCytokinesDisease Models, AnimalDrug DiscoveryHerpes SimplexHerpesvirus 1, HumanHost-Pathogen InteractionsHumansMiceRibavirinRibosomal Protein S6 KinasesRibosomesSignal TransductionAntiviral AgentsBiomarkersCytokinesRibavirinRibosomal Protein S6 KinasesSTAT1 Transcription Factor

Identifiers

PMID31513822
PMCPMC7114107
OpenAlexW2972945400

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.