The roles of signaling pathways in SARS-CoV-2 infection; lessons learned from SARS-CoV and MERS-CoV

Arch Virol. 2021 Mar;166(3):675-696. doi: 10.1007/s00705-021-04958-7. Epub 2021 Jan 18.

Abstract

The number of descriptions of emerging viruses has grown at an unprecedented rate since the beginning of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the third highly pathogenic coronavirus that has introduced itself into the human population in the current era, after SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Molecular and cellular studies of the pathogenesis of this novel coronavirus are still in the early stages of research; however, based on similarities of SARS-CoV-2 to other coronaviruses, it can be hypothesized that the NF-κB, cytokine regulation, ERK, and TNF-α signaling pathways are the likely causes of inflammation at the onset of COVID-19. Several drugs have been prescribed and used to alleviate the adverse effects of these inflammatory cellular signaling pathways, and these might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarize alterations of cellular signaling pathways that are associated with coronavirus infection, particularly SARS-CoV and MERS-CoV, and tabulate the therapeutic agents that are currently approved for treating other human diseases.

Publication types

  • Review

MeSH terms

  • COVID-19 / pathology*
  • COVID-19 Drug Treatment
  • Cytokines / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Inflammation / pathology
  • Middle East Respiratory Syndrome Coronavirus / drug effects
  • Middle East Respiratory Syndrome Coronavirus / metabolism*
  • NF-kappa B / metabolism
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / metabolism*
  • Signal Transduction / physiology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • NF-kappa B
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases