COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity

Cell Signal. 2023 Jan:101:110495. doi: 10.1016/j.cellsig.2022.110495. Epub 2022 Oct 15.

Abstract

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.

Keywords: ACE2; Pathway interactions; SARS-CoV-2; Signaling pathways; Signalomes.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • COVID-19*
  • Comorbidity
  • Cytokine Release Syndrome
  • Humans
  • Pandemics
  • SARS-CoV-2

Substances

  • Angiotensin-Converting Enzyme 2