Ion transport blockers inhibit human rhinovirus 2 release.
Picornavirus replication causes leakage of cytoplasmic K+ and an influx of Na+ and Ca2+. In this study, we have explored the possibility that a blockade of Ca2+ and Na+ influx would reduce rhinovirus production and/or release. The Ca2+-channel blockers, verapamil and diltiazem, as well as the blocker of Na+/H+ exchange and the epithelial Na+ channel, EIPA, inhibited both virus production and release. The effect on virus release was more pronounced than the effect on production, thus raising the possibility that rhinovirus release may serve as a target for antiviral agents. Unexpectedly, our results also showed that the antiviral activity of the Ca2+-channel blockers was not due to the block of Ca2+ influx. Similarly, the antiviral activity of EIPA appeared to be unrelated to the blockade of cellular Na+/H+ exchanger or the epithelial Na+ channel. Potential alternative mechanisms of the antiviral activity of these compounds are discussed.
Gazina
Elena V
EV
Howard Florey Institute, The University of Melbourne, Vic. 3010, Australia. gazina@hfi.unimelb.edu.au
Harrison
David N
DN
Jefferies
Meryem
M
Tan
Heneu
H
Williams
David
D
Anderson
David A
DA
Petrou
Steven
S
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D012229:Rhinovirus / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D002118:Calcium