Evaluation of the antiviral activity against junin virus of macrocyclic trichothecenes produced by the hypocrealean epibiont of Baccharis coridifolia

Abstract

Four macrocyclic trichothecenes, roridin A, roridin E, verrucarin A and verrucarin J, produced by the hypocrealean epibiont of Baccharis coridifolia, were evaluated for their inhibitory activity against the arenavirus Junin (JUNV), the etiological agent of Argentine hemorrhagic fever. The trichothecenes achieved a dose-dependent inhibition of JUNV multiplication at concentrations not affecting cell viability. The 50% inhibitory concentration (IC50) values determined by a virus yield inhibition assay were in the range 1.2-4.9 ng/ml. The most active compound was verrucarin J which reduced JUNV yield more than 2 log units and had a similar effect against the arenavirus Tacaribe. The trichothecenes lacked virucidal effects on JUNV virions. From time of addition and removal experiments, it can be concluded that verrucarin J inhibited a late stage in the replicative cycle of JUNV, after 5 h of adsorption.