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7940940 
Journal Article 
Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication 
Wilson, L; Gage, P; Ewart, G 
2006 
1 
Virology
ISSN: 0042-6822 
353 
2 
294-306 
English 
16815524 
WOS:000240930900005 
All coronaviruses encode a small hydrophobic envelope (E) protein, which mediates viral assembly and morphogenesis by an unknown mechanism. We have previously shown that the E protein from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) forms cation-selective ion channels in planar lipid bilayers (Wilson, L., McKinlay, C., Gage, P., Ewart, G., 2004. SARS coronavirus E protein forms cation-selective ion channels. Virology 330(1), 322-331). We now report that three other E proteins also form cation-selective ion channels. These E proteins were from coronaviruses representative of taxonomic groups 1-3: human coronavirus 229E (HCoV-229E), mouse hepatitis virus (MHV), and infectious bronchitis virus (IBV), respectively. It appears, therefore, that coronavirus E proteins in general, belong to the virus ion channels family. Hexamethylene amiloride (HMA)--an inhibitor of the HIV-1 Vpu virus ion channel--inhibited the HCoV-229E and MHV E protein ion channel conductance in bilayers and also inhibited replication of the parent coronaviruses in cultured cells, as determined by plaque assay. Conversely, HMA had no antiviral effect on a recombinant MHV with the entire coding region of E protein deleted (MHVDeltaE). Taken together, the data provide evidence of a link between inhibition of E protein ion channel activity and the antiviral activity of HMA. 
Amiloride; Antiviral compound; Coronavirus; E protein; Hexamethylene amiloride (HMA); Human coronavirus 229E (HCoV-229E); Infectious bronchitis virus (IBV); Ion channel; Mouse hepatitis virus (MHV)