Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies

Autoimmun Rev. 2020 Jul;19(7):102571. doi: 10.1016/j.autrev.2020.102571. Epub 2020 May 3.

Abstract

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has posed a serious threat to global health. As no specific therapeutics are yet available to control disease evolution, more in-depth understanding of the pathogenic mechanisms induced by SARS-CoV-2 will help to characterize new targets for the management of COVID-19. The present study identified a specific set of biological pathways altered in primary human lung epithelium upon SARS-CoV-2 infection, and a comparison with SARS-CoV from the 2003 pandemic was studied. The transcriptomic profiles were also exploited as possible novel therapeutic targets, and anti-signature perturbation analysis predicted potential drugs to control disease progression. Among them, Mitogen-activated protein kinase kinase (MEK), serine-threonine kinase (AKT), mammalian target of rapamycin (mTOR) and I kappa B Kinase (IKK) inhibitors emerged as candidate drugs. Finally, sex-specific differences that may underlie the higher COVID-19 mortality in men are proposed.

Keywords: Bioinformatics; COVID-19; Coronavirus; Pathogenesis; SARS; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Betacoronavirus
  • COVID-19
  • Cells, Cultured
  • Coronavirus Infections / genetics*
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / pathology
  • Drug Discovery
  • Epithelial Cells / virology
  • Female
  • Humans
  • Lung / cytology
  • Male
  • Pandemics
  • Pneumonia, Viral / genetics*
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / pathology
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome
  • Sex Factors*
  • TOR Serine-Threonine Kinases
  • Transcriptome

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases