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

The fact that SARS-CoV ETM forms only pentamers in dodecylphosphocholine (DPC) and perfluorooctanoic (PFO) micelles [38] , strongly suggests that the ion channel activity of coronavirus E proteins is caused by a pentameric ion channel. Therefore, in the present work our aim was (i) to use NMR to determine the structure of the pentameric oligomer formed by a selectively labeled SARS-CoV ETM (residues 8 to 38) when reconstituted in DPC micelles, (ii) to characterize the interaction of HMA or amiloride with this channel, and (iii) to test if this data is still relevant in a more physiological environment, using patch clamped mammalian cells expressing full length SARS-CoV E. The structural model described for this channel provides a valuable insight into coronavirus envelope ion channel activity, ion selectivity and channel inhibition, and could serve as a platform for the development of novel anti-viral drugs.