Abstract
The envelope (E) protein of the SARS-CoV-2 virus forms cation-conducting channels in the endoplasmic reticulum Golgi intermediate compartment (ERGIC) of infected cells. The calcium channel activity of E is associated with the inflammatory responses of COVID-19. Using solid-state NMR (ssNMR) spectroscopy, we have determined the open-state structure of E's transmembrane domain (ETM) in lipid bilayers. Compared to the closed state, open ETM has an expansive water-filled amino-terminal chamber capped by key glutamate and threonine residues, a loose phenylalanine aromatic belt in the middle, and a constricted polar carboxyl-terminal pore filled with an arginine and a threonine residue. This structure gives insights into how protons and calcium ions are selected by ETM and how they permeate across the hydrophobic gate of this viroporin.