Abstract
Harringtonine (HT) and homoharringtonine (HHT), alkaloid
esters isolated from the genus Cephalotaxus, exhibit antitumor
activity. A semisynthetic HHT has been approved
for treatment of chronic myelogenous leukemia. In addition
to antileukemic activity, HT and HHT are reported to possess
potent antiviral activity. In this study, we investigated
the effects of HT and HHT on replication of varicella-zoster
virus (VZV) in vitro. HT and HHT, but not their biologically
inactive parental alkaloid cephalotaxine (CET), significantly
inhibited replication of recombinant VZV-pOka luciferase.
Furthermore, HT and HHT, but not CET, strongly induced
down-regulation of VZV lytic genes and exerted potent antiviral
effects against a VZV clinical isolate. The collective data
support the utility of HT and HHT as effective antiviral candidates
for treatment of VZV-associated diseases.
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