Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature

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 immunemediated 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.

Mutational insights into the envelope protein of SARS-CoV-2

“…Although, the mutational spectra of different structural proteins (S, M, and N) of SARS-CoV-2 has been reported by several research groups ( Islam et al, 2020 ; Pachetti et al, 2020 ; Phan, 2020 ; Rahman et al, 2020b ; Rahman et al, 2020c ) over a short period of time, however, available literature on the nucleotide and aa-level mutations of E protein is till limited. However, the sequence identity between the E proteins of SARS-CoV and SARS-CoV-2 sturdily recommends the conservation of its functional features, thereby playing nearly identical roles in the pathogenesis of COVID-19 ( Schoeman and Fielding, 2020 ). Indeed, a great discrepancy exists in the amino acid sequences of the E protein between the different coronavirus groups and, to an extent, within some of the groups.…”

Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1

“…Specifically, we used 2D class averaging for initial particle cleanup which resulted in 2,193,282 particles. Among these particles, we produced an initial 3D model using CryoSPARC and used the model to perform 3D classifications in Relion3 for five classes with a pixel size of 2.736 Å (Fig.…”

Delivery of recombinant SARS-CoV-2 envelope protein into human cells

“…However, its importance is highlighted by cellular studies showing that the CoV E and M proteins alone are sufficient to produce a budding virus-like particle (VLP) (10–12). Moreover, deletion of E drastically lowers viral fitness (13–15) and growing evidence suggests that E is directly responsible for acute respiratory distress syndrome (ARDS) occurring in conjunction with CoV infections (16). E is highly expressed in infected cells, but only a small fraction is incorporated into mature viral particles, implying functions beyond its role as a mature capsid structural protein (17).…”