It is a small homopentameric membrane protein (75 amino-acids per protomer) [180], which has been shown to be essential for viral particle assembly in SARS-CoV [51]. The N-terminal region of the protein spans the lipid bilayer twice, while the C-terminal is exposed to the interior of the virus [181,182]. In IBV and SARS-CoV, the E protein interacts with the viral M protein through an undefined region [183,184]; and also with the host Protein Associated with Lin Seven 1 (PALS1), a factor associated to the pathogenesis [185], thought the E protein C-terminal. Also, in many CoVs, the E protein works as an ion-channelling viroporin [180], which affects the production of cytokines, and in consequence the inflammatory response [186]. While there is no structural data available for the SARS-CoV-2 E protein, the structure of the TM region of the SARS-CoV homopentamer is available (residues 8-65) (PDB 5X29). Within that region, e corresponding E proteins share 91% sequence identity, and 98% sequence similarity. The homology model of the SARS-CoV-2 E protein is shown in Figure S12. Based on structural andfunctional considerations, the E protein channel would be the primary target site for drug development. In fact, hexamethylene amiloride (HMA) has been reported to bind to the SARS-CoV E protein homopentamer, but not to an isolated protomer [187].
Its a long paper getting into all aspects of Covid targets, the above is the relevant section that may interest BIT holders. note : Hexamethylene amiloride (HMA) analogue (BIT225)
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