FIGURE 2.

A summary of the role that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein plays in the immunopathology of severe coronavirus disease 2019 (COVID-19) cases. The E protein can induce a cytokine storm through protein-protein interaction (PPI) with the host protein syntenin and is mediated by the last four residues of the E protein which constitute the PDZ-binding motif (PBM). This activates the p38 MAPK signaling pathway, triggering the release of inflammatory cytokines. The E protein can also stimulate the release of the inflammatory cytokine interleukin (IL)-1β through its ion-channel (IC) activity. It forms a viroporin that can channel calcium ions (Ca²⁺), which activates the NLRP3 inflammasome that produces IL-1β. The resulting cytokine storm is responsible for the immune-mediated pathology often seen in severe COVID-19 cases and give rise to complications such as pulmonary edema and the acute respiratory distress syndrome (ARDS).