Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective

Int J Biol Macromol. 2020 Nov 15:163:1-8. doi: 10.1016/j.ijbiomac.2020.06.228. Epub 2020 Jun 26.

Abstract

The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome. Network topological analysis discovers 15 SARS-CoV-2 targets, which belongs to a subset of interferon (IFN) stimulated genes (ISGs). These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19. We have identified significant interaction between ISGs and TLR3 agonists, like poly I: C, and imiquimod, and suggests that TLR3 agonists can be considered as a potential drug for drug repurposing in COVID-19. Our network centric analysis suggests that moderating the innate immune response is a valuable approach to target COVID-19.

Keywords: COVID-19; Drug repurposing; Immune response; Interferon stimulating genes; Network biology.

MeSH terms

  • A549 Cells
  • Antiviral Agents / pharmacology
  • Betacoronavirus / genetics*
  • Betacoronavirus / immunology
  • COVID-19
  • Coronavirus Infections / genetics*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Drug Repositioning
  • ELAV-Like Protein 2 / genetics*
  • ELAV-Like Protein 2 / immunology
  • ELAV-Like Protein 2 / metabolism*
  • Gene Regulatory Networks
  • Humans
  • Immunity, Innate
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Pandemics
  • Pneumonia, Viral / genetics*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Protein Interaction Maps / genetics
  • SARS-CoV-2
  • Signal Transduction
  • Transcriptome

Substances

  • Antiviral Agents
  • ELAV-Like Protein 2
  • ELAVL2 protein, human
  • Interferon-gamma