Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel

Pervushin, Konstantin; Tan, Edward; Parthasarathy, Krupakar; Lin, Xin; Jiang, Feng Li; Yu, Dejie; Vararattanavech, Ardcharaporn; Soong, Tuck Wah; Liu, Ding Xiang; Torres, Jaume

All coronaviruses express the envelope (E) protein, a typically short polypeptide that in SARS-CoV is 76 amino acids long, and which contains at least one a-helical transmembrane domain (ETM). In SARS-CoV E the transmembrane domain spans ,25 residues [21] , approximately from residue 10 to 35 . Coronavirus E proteins are incorporated into the virion lipidic envelope, along with the spike protein (S) and the membrane protein (M). While the S protein is involved in fusion with host membranes during entry into cells, and the M protein is important in envelope formation and budding, E protein is not essential for in vitro and in vivo coronavirus replication. However, its absence results in an attenuated virus, as shown for SARS-CoV [22] . Recently, using a transgenic mouse model expressing the SARS-CoV receptor human angiotensin converting enzyme-2 (hACE-2), SARS coronavirus lacking gene E was shown to be attenuated and, in contrast to the wild type virus, did not grow in the central nervous system [23] . In other coronaviruses, E protein affects viral morphogenesis, i.e., virus-like particle (VLP) formation and release [24] [25] [26] [27] [28] [29] . Indeed, mutations in the extramembrane domain of E protein impaired viral assembly and maturation in MHV [30] . In TGEV, the absence of E protein resulted in a blockade of virus trafficking in the secretory pathway and prevention of virus maturation [31, 32] .