Myristic acid analogs are inhibitors of Junin virus replication

The effects of two myristic acid analogs on Junin virus UV) replication wer e investigated. The compounds chosen for the study were DL-2-hydroxymyristi c acid (2OHM), an inhibitor of N-myristoyltransferase (NMT), which binds th e enzyme and blocks protein myristoylation, and 13-oxamyristic acid (13OM), a competitive inhibitor of NMT which incorporates into the protein instead of myristic acid. Both types of analogs achieved dose-dependent inhibition of viral multiplication at concentrations not affecting cell viability. Th e 50% inhibitory concentration values determined by a virus-yield inhibitio n assay for different strains of JV, including a human pathogenic strain, a nd for the related arenavirus, Tacaribe, were in the range 1.6 to 20.1 mu M , with 13OM as the most active compound. From time of addition and removal experiments, it can be concluded that both analogs inhibit a late stage in the JV replicative cycle, and their effect was partially reversible. The cy toplasmic and surface expression of JV glycoproteins was not affected in th e presence of the compounds, as revealed by immunofluorescence staining, su ggesting that JV glycoprotein myristoylation would not be essential for the intracellular transport of the envelope proteins, but it may have an impor tant role in their interaction with the plasma membrane during virus buddin g. (C) Elsevier, Paris.