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 3D structure of the pentameric channel formed by the transmembrane domain of SARS-CoV E (ETM) was reconstructed in several stages (Fig. S1 , A-C). In a first stage, the structure of the ETM monomer was calculated using the constraints derived from 492 NOEs. For a set of 20 ETM monomeric conformers, the backbone root-mean-square deviation (RMSD) was less than 1 Ã… , or 1.5 Ã… after including side chain heavy atoms (see statistics in Table S1 ). ETM forms a continuous a-helix encompassing all residues ( Fig. 1 , A-C), including both N-and C-termini, showing no signs of terminal fraying [39] . Similar results were obtained in the presence of the drugs HMA and amantadine (AMT) (Fig. S2 ). The latter drug was shown to inhibit in vitro channel activity of a transmembrane domain of SARS-CoV ETM flanked by two Nand C-terminal lysines [37] .