Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

Front Immunol. 2020 Jun 10:11:1372. doi: 10.3389/fimmu.2020.01372. eCollection 2020.

Abstract

Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.

Keywords: COVID-19; SARS-CoV-2; antiviral immunity; interferon-induced transmembrane proteins; valproic acid.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • Animals
  • Antiviral Agents / pharmacology
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus Infections / genetics*
  • Coronavirus Infections / immunology*
  • Disease Models, Animal
  • Ferrets
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunity, Innate
  • Lung
  • Macaca fascicularis
  • Membrane Proteins / genetics*
  • Mice
  • Myxovirus Resistance Proteins / genetics
  • Pandemics
  • Pneumonia, Viral / genetics*
  • Pneumonia, Viral / immunology*
  • RNA-Binding Proteins / genetics*
  • SARS-CoV-2
  • Species Specificity
  • Up-Regulation / drug effects
  • Valproic Acid / pharmacology

Substances

  • Antiviral Agents
  • IFITM3 protein, human
  • Membrane Proteins
  • Myxovirus Resistance Proteins
  • RNA-Binding Proteins
  • Valproic Acid
  • 2',5'-Oligoadenylate Synthetase