Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication
dc.contributor.author | Wilson, Lauren | |
dc.contributor.author | Gage, Peter | |
dc.contributor.author | Ewart, Gary | |
dc.date.accessioned | 2015-12-07T22:33:05Z | |
dc.date.issued | 2006 | |
dc.date.updated | 2015-12-07T10:27:14Z | |
dc.description.abstract | 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 (MHVΔE). Taken together, the data provide evidence of a link between inhibition of E protein ion channel activity and the antiviral activity of HMA. | |
dc.identifier.issn | 0042-6822 | |
dc.identifier.uri | http://hdl.handle.net/1885/23103 | |
dc.publisher | Academic Press | |
dc.source | Virology | |
dc.subject | Keywords: amiloride derivative; hexamethylene amiloride; ion channel; unclassified drug; virus protein; virus protein e; animal cell; antiviral activity; article; Avian infectious bronchitis virus; cell culture; controlled study; Coronavirus; Murine hepatitis coron Amiloride; Antiviral compound; Coronavirus; E protein; Hexamethylene amiloride (HMA); Human coronavirus 229E (HCoV-229E); Infectious bronchitis virus (IBV); Ion channel; Mouse hepatitis virus (MHV) | |
dc.title | Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication | |
dc.type | Journal article | |
local.bibliographicCitation.lastpage | 306 | |
local.bibliographicCitation.startpage | 294 | |
local.contributor.affiliation | Wilson, Lauren, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Gage, Peter, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Ewart, Gary, Biotron Ltd | |
local.contributor.authoremail | repository.admin@anu.edu.au | |
local.contributor.authoruid | Wilson, Lauren, u9715160 | |
local.contributor.authoruid | Gage, Peter, u8404889 | |
local.description.embargo | 2037-12-31 | |
local.description.notes | Imported from ARIES | |
local.identifier.absfor | 119999 - Medical and Health Sciences not elsewhere classified | |
local.identifier.ariespublication | u4020362xPUB25 | |
local.identifier.citationvolume | 353 | |
local.identifier.doi | 10.1016/j.virol.2006.05.028 | |
local.identifier.scopusID | 2-s2.0-33748714028 | |
local.identifier.uidSubmittedBy | u4020362 | |
local.type.status | Published Version |
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