Inhibition of varicella-zoster virus replication by an inhibitor of protein myristoylation.
Inhibitors of myristoylation and analogues of myristic acid inhibit the replication of some retroviruses including human immunodeficiency virus, but no studies with other virus families have been reported. We have shown that replication of varicella-zoster virus (VZV) in tissue is inhibited by DL-2-hydroxymyristic acid at concentrations similar to those required for inhibition with acyclovir. Protein synthesis is not inhibited, but protein myristoylation is non-specifically reduced. Despite this lack of specificity, DL-2-hydroxymyristic acid inhibits VZV replication without apparent cytotoxicity. This is in agreement with our earlier suggestion that non-specific inhibitors of myristoylation could have antiviral effects without toxicity to cells due to the stability of cellular myristoylproteins. This supports suggestions that myristoylation inhibitors have potential as antiviral drugs against the many viruses that produce myristoylproteins.
Medical College, St Bartholomew's Hospital, London, U.K.
D R
DR
Harper
R L
RL
Gilbert
C
C
Blunt
R A
RA
McIlhinney
D000212:Acyclovir / Q000494:pharmacology; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000254:growth & development; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009227:Myristic Acids; D019814:Myristic Acid; C017418:alpha-hydroxymyristic acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D000212:Acyclovir