Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication
Autor: | Lauren Elizabeth Wilson, Peter W. Gage, Gary Ewart |
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Rok vydání: | 2006 |
Předmět: |
Mouse hepatitis virus (MHV)
Human coronavirus 229E viruses Molecular Sequence Data Virus Replication medicine.disease_cause Antiviral Agents Ion Channels Article Virus Cell Line Amiloride Mice Mouse hepatitis virus Viral Envelope Proteins Infectious bronchitis virus (IBV) Hexamethylene amiloride (HMA) Virology medicine Animals Humans Amino Acid Sequence Ion channel Coronavirus E protein Virus quantification biology virus diseases Antiviral compound biology.organism_classification Human coronavirus 229E (HCoV-229E) Avian infectious bronchitis virus Ion Channel Gating Sodium Channel Blockers medicine.drug |
Zdroj: | Virology |
ISSN: | 0042-6822 |
DOI: | 10.1016/j.virol.2006.05.028 |
Popis: | 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. |
Databáze: | OpenAIRE |
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