Abstract
Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1β and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1β and IL-6 in severe cases can improve patient outcome.
Highlights
Coronaviruses (CoVs) all have positive sense, single-stranded RNA genomes that range in size between 26 and 32 kb (Gorbalenya et al, 2006; Corman et al, 2018)
Based on the literature for the pathogenic human CoVs (hCoVs), severe acute respiratory syndrome (SARS)-CoV and Middle East respiratoryEnvelope Protein and Immunopathology syndrome (MERS)-CoV, we propose that the PDZ-Binding Motif (PBM) and IC activity of SARS-CoV-2 E is very likely responsible for the cytokine storm induction and the consequent immunopathology often seen in severe COVID-19 cases (Figure 2)
Much progress has been made in hCoV research, the novelty of SARS-CoV-2 clearly leaves much still to be answered
Summary
Coronaviruses (CoVs) (order Nidovirales) all have positive sense, single-stranded RNA genomes that range in size between 26 and 32 kb (Gorbalenya et al, 2006; Corman et al, 2018). Patients infected with SARS-CoV present with symptoms resembling atypical pneumonia, exhibiting fever, chills, headache, malaise, myalgia, and dry cough (Lee et al, 2003; Peiris et al, 2003a,b) Those infected with MERS-CoV report similar nonspecific symptoms, but demonstrate a much higher case-fatality rate, for elderly persons and those with underlying medical conditions (Assiri et al, 2013a,b; Saad et al, 2014). Some viral proteins, especially those involved in pathogenesis, adversely affect the host cell and can be directly implicated in the development of symptoms and, the clinical presentation (Manjarrez-Zavala et al, 2013) Viruses by their very nature rely entirely on their host cells for replication, propagation, and, survival which is achieved by subverting the protein-protein interaction (PPI) networks of their host cells (Gladue et al, 2012; Guth and Sodroski, 2014; Brito and Pinney, 2017). Data on the role of E exists predominantly for the prototypic SARSCoV, which has been studied the most extensively, with some studies for MERS-CoV E
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