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

In recent years, several viral proteins have shown membrane permeabilization properties or ion channel activity, e.g., poliovirus 2B, alphavirus 6 K, HIV-1 Vpu, and influenza virus M2, and have been named collectively as 'viroporins' [52] . However, the physiological relevance of this activity has only been shown conclusively for M2, a well known pharmacological target that is inhibited by AMT for which a detailed structure is available [53] [54] [55] . Electrophysiological data, as well as detailed structural information is lacking for most of these proteins. We show in the present work that SARS-CoV E possesses channel activity not only in vitro, but also when expressed in mammalian cells, and we have structurally characterized the homo-pentameric transmembrane domain (ETM) responsible for this activity, when solubilized in DPC micelles in the absence or presence of small drugs.