Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission

Abstract

The highly infective coronavirus disease 19 (COVID-19) is caused by a novel strain of coronaviruses – the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – discovered in December 2019 in the city of Wuhan (Hubei Province, China). Remarkably, COVID-19 has rapidly spread across all continents and turned into a public health emergency, which was ultimately declared as a pandemic by the World Health Organization (WHO) in early 2020. SARS-CoV-2 presents similar aspects to other members of the coronavirus family, mainly regarding its genome, protein structure and intracellular mechanisms, that may translate into mild (or even asymptomatic) to severe infectious conditions. Although the mechanistic features underlying the COVID-19 progression have not been fully clarified, current evidence have suggested that SARS-CoV-2 may primarily behave as other β-coronavirus members. To better understand the development and transmission of COVID-19, unveiling the signaling pathways that may be impacted by SARS-CoV-2 infection, at the molecular and cellular levels, is of crucial importance. In this review, we present the main aspects related to the origin, classification, etiology and clinical impact of SARS-CoV-2. Specifically, here we describe the potential mechanisms of cellular interaction and signaling pathways, elicited by functional receptors, in major targeted tissues/organs from the respiratory, gastrointestinal (GI), cardiovascular, renal, and nervous systems. Furthermore, the potential involvement of these signaling pathways in evoking the onset and progression of COVID-19 symptoms in these organ systems are presently discussed. A brief description of future perspectives related to potential COVID-19 treatments is also highlighted.

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

“…For this reason, the RAS system appears to have a central role in SARS-CoV-2 infection and canonical ACE2 pathway links multiple organ damage in COVID-19. Since SARS-CoV-2 induces ACE2 depletion, it leads to a more extensive conversion of Ang-I into Ang-II via ACE, which then binds to ATR1 receptors ( Battagello et al, 2020 ). When ATR1 is stimulated, this latter in turn stimulates HDAC to up-regulate ACE2 expression and synthesis facilitating SARS-CoV-2 infection.…”

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

“…In this pathway, renin generated in the kidneys cleaves angiotensinogen from the liver, producing Ang I and then is cleaved by ACE into Ang-II (the substrate of ACE2). Ang I binds to the AT1R and AT2R as well as the RAS system has an important function in SARS-CoV-2 infection ( Battagello et al, 2020 ).…”

“…As previously mentioned, SARS-CoV-2 enters the CNS via the ACE2 or TMPRSS2 receptors ( El Tabaa and El Tabaa, 2020 ; Nemoto et al, 2020 ). In order to decline SARS-CoV-2 entry to neural cells, ACE2 activity should be declined ( Battagello et al, 2020 ). Spike (S) glycoprotein as the main SARS-CoV-2 structural protein with a critical role in binding to the host cell and protecting the virus against some of the host species antibodies, is another target of phytochemicals ( Schoeman and Fielding, 2019 ).…”

Laboratory-Based Resources for COVID-19 Diagnostics: Traditional Tools and Novel Technologies. A Perspective of Personalized Medicine

“…For example, Battagello et al [ 93 ] summarized data on the significance of cellular stress signals during penetration and into the cell and replication of SARS-CoV-2 and concluded that the appearance of clinical symptoms in individual patients depended on the predominant lesion and invasion of the virus into cells, where ACE2 is considered the main receptor for the protein spike (S-protein), through which the virus can attach to the target cells [ 93 ].…”