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

• Published in: Antiviral chemistry & chemotherapy Vol. 5; no. 3; pp. 182 - 186
• Main Authors: Gilbert, R. L., Blunt, C. J., Harper, D. R., Jeffries, D. J., Mcllhinney, R. A. J.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.1994; International Medical Press; Sage Publications Ltd
• Subjects: Acids; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chicken pox; Cytotoxicity; Enantiomers; HIV; Human immunodeficiency virus; Medical sciences; Myristoylation; N-Myristoyltransferase; Pharmacology. Drug treatments; Replication; Varicella; varicella-zoster virus; Viruses; Varicella zoster virus; Acyltransferases; Enzyme; Herpesviridae; Transferases; Alphaherpesvirinae; Enzyme inhibitor; Cytotoxicity; Virus; Glycylpeptide N-tetradecanoyltransferase; Structure activity relation; Antiviral; Replication; Mechanism of action
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632029400500307

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 VZV replication. One of these was N-myristoylglycinaldiethylacetal (GoA), which has been reported to be active against HIV. 12-(methoxy) dodecanoic acid (13-oxamyristic acid), which has also been reported to inhibit HIV replication, was found to inhibit VZV replication but was cytotoxic at high concentrations. The greatest inhibitory effect without apparent toxicity was induced by 2-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.