17-allylamino-17-(demethoxy)geldanamycin (17-AAG) is a potent and effective inhibitor of human cytomegalovirus replication in primary fibroblast cells

Arch Virol. 2012 Oct;157(10):1971-4. doi: 10.1007/s00705-012-1379-7. Epub 2012 Jun 19.

Abstract

The 90 % human cytomegalovirus inhibitory concentration of 17-allylamino-17-(demethoxy)geldanamycin (17-AAG) was 0.1 nM and 50 % cytotoxicity required at least a 10 μM concentration. Three molecular targets may explain the antiviral activities of this compound. These are (1) heat shock protein maturation complexes, (2) host cell cycle progression and (3) phosphatidylinositol 3-kinase signaling. However, the data suggested a mechanism of action where 17-AAG blocked immediate-early protein transactivation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Benzoquinones / pharmacology*
  • Cells, Cultured
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / metabolism
  • Cytomegalovirus / physiology
  • Fibroblasts / virology
  • Humans
  • Immediate-Early Proteins / antagonists & inhibitors*
  • Immediate-Early Proteins / metabolism
  • Lactams, Macrocyclic / pharmacology*
  • Transcriptional Activation / drug effects
  • Virus Replication / drug effects*

Substances

  • Benzoquinones
  • Immediate-Early Proteins
  • Lactams, Macrocyclic
  • tanespimycin