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 a previous report [36] , it was suggested that synthetic CoV E proteins have cation selective channel activity, with selectivity (P Na /P K ) of 0.25 for HCoV-229E, 69 for MHV E, 10 for SARS- CoV E and 3 for IBV. In the present work, we observed a very mild preference for sodium over potassium. According to these data, only the apparent selectivity of HMV for sodium appears to be significant. The diameter of naked Na + is around 2 Ã… , and that of K + is 2.66 Ã… , and the diameter of the ETM pore at the level of N15 (4 to 5 Ã… ) is sufficient to accommodate a single dehydrated Na + or K + ion. Hence it may be speculated that N15, or its polar equivalent in other sequences, form a selectivity filter for cations. The equivalent residue to SARS-CoV E N15 in MHV E is Gln (Fig. S7) , which has a one methylene longer side chain. This may lead to further occlusion of the channel at this position, and may explain the observed higher selectivity for sodium in MHV E. We also note that the lumen-facing orientation of Asn and Gln may also have a structural role, as these residues are known to stabilize transmembrane interactions [44] [45] [46] .