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

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

Kenneth Lundstrom  1 , Altijana Hromić-Jahjefendić  2 , Esma Bilajac  3 , Alaa A A Aljabali  4 , Katarina Baralić  5 , Nagwa A Sabri  6 , Eslam M Shehata  7 , Mohamed Raslan  8 , Ana Cláudia B H Ferreira  9 , Lidiane Orlandi  10 , Ángel Serrano-Aroca  11 , Murtaza M Tambuwala  12 , Vladimir N Uversky  13 , Vasco Azevedo  14 , Khalid J Alzahrani  15 , Khalaf F Alsharif  16 , Ibrahim F Halawani  17 , Fuad M Alzahrani  18 , Elrashdy M Redwan  19 , Debmalya Barh  20
Affiliations
Review

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

Kenneth Lundstrom et al. Cell Signal. 2023 Jan.

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.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Overview of the SARS-CoV-2 infection mechanism and the post-infection host immune responses. The diagram illustrates the role of TMPRSS2, ACE-2, and CD147 during SARS CoV-2 infection, innate and adaptive immunity, and SARS-CoV-2 viral entry via receptors. Host immune defense begins early with the initiation of PRR signaling (TLRs, RLRs, CLRs and cGAS-STING) leading to activation of type I IFN along with proinflammatory cytokines [29]. The figure has been created using BioRender (www.biorender.com)
Fig. 2
Fig. 2
Summary of signaling pathways deregulated in host tissues and organs. The figure has been created using BioRender (www.biorender.com)
Fig. 3
Fig. 3
Pathway-pathway interactions in COVID-19-associated comorbidity and long-term consequences with the focus on different diseases. The figure has been created using BioRender (www.biorender.com)
Fig. 4
Fig. 4
Overview of SARS-CoV-2 signaling in cell proliferation and apoptosis. The figure has been created using BioRender (www.biorender.com)
See this image and copyright information in PMC

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