COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity
Kenneth Lundström, Altijana Hromić‐Jahjefendić, Esma Bilajac, Alaa A. A. Aljabali, Katarina Baralić, Nagwa A. Sabri, Eslam M. Shehata, Mohamed Raslan, Ana Cláudia Barbosa Honório Ferreira, Lidiane Orlandi, Ángel Serrano‐Aroca, Murtaza M. Tambuwala, Vladimir N. Uversky, Vasco Azevedo, Khalid J. Alzahrani, Khalaf F. Alsharif, Ibrahim F. Halawani, Fuad M. Alzahrani, Elrashdy M. Redwan, Debmalya Barh
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.