Viroporin Structure. Viroporins localise to intracellular membranes and possess at least one membrane spanning domain. They are divided into classes depending on the number of trans-membrane domains (TMDs). IAV M2 is a Class IA viroporin with a single TMD, a luminal N-terminus and C-terminal cytoplasmic tail. Vpu, also a class IA viroporin, is comprised of a short N-terminal domain, a hydrophobic TMD and a longer cytoplasmic domain, which includes the hinge region and two α-helical domains. HCV p7 is a class IIA viroporin with two transmembrane domains and luminal N and C termini. HPV-16 E5 and SARS-Co-V ORF3a are both class III viroporins with three membrane-spanning domains while SARS-CoV ORF3a has a long cytoplasmic tail.