Meta-Biol

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This SARS-CoV-2 event was manually inferred from the event of homologous SARS-CoV-1 E protein, which forms Ca2+ permeable protein‑lipid channels in ERGIC/Golgi membranes (Nieto‑Torres JL et al. 2015). The E protein of SARS-CoV-2 shares a high level of homology with SARS-CoV-1 (Cao Y et al. 2021). NMR spectroscopy identified the pentameric structure of transmembrane domain of SARS‐CoV‐2 E protein in lipid bilayers (Mandala VS et al. 2020). Further, hexamethylene amiloride (HMA), an ion channel blocker, was found to bind to the N-terminal region of SARS-CoV-2 E protein and reduced infection in SARS-CoV-2-infected African green monkey kidney Vero E6 cells (Park SH et al. 2021). Computational electrophysiology simulations further confirmed that the E protein forms a functional ion channel (Cao Y et al. 2020). Release of Ca2+ from ERGIC/Golgi lumen to the cytosol disrupts Ca2+ balance within cells contributing to the activation of the NLRP3 inflammasome (reviewed by Zhou Y et al. 2020).

This Reactome event describes the ion channel activity of the SARS-CoV-2 E protein, although it remains to be shown in vivo.