Effect of Inhibitors of Protein Myristoylation on Varicella-Zoster Virus Replication

Inhibitors of N-myristoyltransferase (NMT) have been shown to inhibit retrovirus replication, notably that of the human immunodeficiency virus (HIV), where the absence of protein myristoylation inhibits viral replication. The authors have assayed 14 compounds derived from myristic acid for activity against varicella-zoster virus (human herpesvirus 3; VZV) by plaque reduction assay. Seven showed cytotoxicity and of the others, two failed to inhibit VN replication. One of these was N-myristoylglycinaldiethylacetal (GoA), which has been reported to be active against HIV. 12-(methoxy) dodecanoic acid (13-oxamyrisitic acid), which has also been reported to inhibit HIV replication, was found to inhibit VN replication but was cytotoxic at high concentrations. The greatest inhibitory effect without apparent toxicity was induced by 5-hydroxytetradecanoic acid and its enantiomers. The results of these assays provide further evidence that inhibitors of NMT have potential as antiviral agents against the many viruses with myristoylated proteins.