Envelop protein (E) The E protein is the smallest (8.4–12 kDa size) TM structural protein of CoV.[5859] Two distinct domains comprise the E protein: the hydrophobic domain and the charged cytoplasmic tail. However, the structure is highly variable among different members of the CoV family.[59] The E protein has a special role in viral morphogenesis, especially during assembly and egress.[59] CoVs lacking E protein show lower viral titer, immature, and inefficient progenies.[5860] Oligomerization of E proteins leads to the formation of ion channels.[61] However, the importance of these ion channels is still not clear. Many other studies infer that the E protein acts in coordination with other intracellular proteins and modulates the activity of those proteins.[59] E protein also acts as a virulence factor.[59] E protein has an important role in CoV assembly and budding formation.[24] Apart from this, E protein found around the ER and Golgi body regions.[60] Hexamethylene amiloride blocks this E protein-associated ion channel activity in the mammalian cells expressing SERS-CoV envelop protein.[62]