Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease

Viruses. 2021 Aug 4;13(8):1540. doi: 10.3390/v13081540.

Abstract

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

Keywords: Dengue fever disease; common mechanisms of action; in silico evaluation of drugs; multi-tissue transcriptomics; tissue specialization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adrenergic Antagonists / pharmacology
  • Adrenergic Antagonists / therapeutic use
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Brain / metabolism
  • Computer Simulation
  • Dengue / blood
  • Dengue / drug therapy*
  • Dengue / genetics
  • Dengue / metabolism
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Drug Repositioning
  • Humans
  • Liver / metabolism
  • Metabolic Networks and Pathways / drug effects
  • NF-kappa B / metabolism
  • Serotonin Antagonists / pharmacology
  • Serotonin Antagonists / therapeutic use
  • Severe Dengue / blood
  • Severe Dengue / drug therapy
  • Severe Dengue / genetics
  • Severe Dengue / metabolism
  • Spleen / metabolism
  • Transcriptome*

Substances

  • Adrenergic Antagonists
  • Antiviral Agents
  • NF-kappa B
  • Serotonin Antagonists
  • Adenosine Triphosphatases