Amiloride Derivatives Inhibit Coxsackievirus B3 RNA Replication

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2007 Nov 23

PMID 18032495

Citations 25

Authors

David N Harrison

Elena V Gazina

Damian F Purcell

David A Anderson

Steven Petrou

Affiliations

Soon will be listed here.

Abstract

Amiloride derivatives are known blockers of the cellular Na(+)/H(+) exchanger and the epithelial Na(+) channel. More recent studies demonstrate that they also inhibit ion channels formed by a number of viral proteins. We previously reported that 5-(N-ethyl-N-isopropyl)amiloride (EIPA) modestly inhibits intracellular replication and, to a larger extent, release of human rhinovirus 2 (HRV2) (E. V. Gazina, D. N. Harrison, M. Jefferies, H. Tan, D. Williams, D. A. Anderson and S. Petrou, Antiviral Res. 67:98-106, 2005). Here, we demonstrate that amiloride and EIPA strongly inhibit coxsackievirus B3 (CVB3) RNA replication and do not inhibit CVB3 release, in contrast to our previous findings on HRV2. Passaging of plasmid-derived CVB3 in the presence of amiloride generated mutant viruses with amino acid substitutions in position 299 or 372 of the CVB3 polymerase. Introduction of either of these mutations into the CVB3 plasmid produced resistance to amiloride and EIPA, suggesting that they act as inhibitors of CVB3 polymerase, a novel mechanism of antiviral activity for these compounds.

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