Envelope (E) viroporin protein, ORF5, of 75 aas and 1 N-terminal TMS. The E-proteins of CoV, CoV-2 and MERS oligomerize to form homopentamers by aligning their TMSs into a pore-forming complex in phospholipid membranes (Surya et al. 2015). The pore is weakly cation selective with Ca2+ favored over K+, and Na+ favored over H+ (Castaño-Rodriguez et al. 2018). It is involved in various aspects of the virus life cycle including assembly, budding, envelope formation, virus release, and inflammasome activation (Breitinger et al. 2021). The structure and drug binding of the SARS-CoV-2 Envelope (E) protein in phospholipid bilayers has been determined (Hong et al. 2020). E forms a five-helix bundle surrounding a narrow central pore. The middle of the TM segment is distorted from the ideal α-helical geometry due to three regularly spaced phenylalanine residues, which stack within each helix and between neighboring helices. These aromatic interactions, together with interhelical Val and Leu interdigitation, cause a dehydrated pore compared to the viroporins of influenza and HIV viruses. Hexamethylene amiloride and amantadine bind shallowly to polar residues at the N-terminal lumen, while acidic pH affects the C-terminal conformation. Thus, SARS-CoV-2 E forms a structurally robust but bipartite channel whose N- and C-terminal halves can interact with drugs, ions and other viral and host proteins semi-independently (Hong et al. 2020). Mandala et al. 2020 reported a 2.1-Å structure and the drug-binding site of E's transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal alpha-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs (Mandala et al. 2020). Chenodeoxycholate(CDC) and ursodeoxycholate (UDC) bind to the envelope (E) protein of SARS-Cov2 and serve as candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitating the entry of solvents/polar inhibitors inside the viral cell (Yadav et al. 2020). Interactions of SARS-CoV-2 envelope protein with amilorides promote antiviral activity (Park et al. 2021). E-protein mediated currents were inhibited by amantadine and rimantadine, as well as 5-(N,N-hexamethylene)amiloride (HMA). Of 10 flavonoids, epigallocatechin and quercetin were most effective (Breitinger et al. 2021).
|Protein Name:||Envelope small membrane protein|
|Species:||Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)  |
|Number of TMSs:||1|
|Location1 / Topology2 / Orientation3:
Host Golgi apparatus membrane1 / Single-pass type III membrane protein2
1: MYSFVSEETG TLIVNSVLLF LAFVVFLLVT LAILTALRLC AYCCNIVNVS LVKPSFYVYS
61: RVKNLNSSRV PDLLV