The unique antiviral activity of artesunate is broadly effective against human cytomegaloviruses including therapy-resistant mutants

Sunwen Chou, Gail Marousek, Sabrina Auerochs, Thomas Stamminger, Jens Milbradt, Manfred Marschall

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Current therapy options to treat infections with human cytomegalovirus face severe limitations leading to a continued search for novel drug candidates. Here, we describe novel characteristics of the strong antiviral potency of the drug artesunate. In vitro virus replication systems were applied to analyze a number of laboratory and clinically relevant strains of human cytomegalovirus. An inhibitory block at a very early stage of infection was demonstrated. Time-of-addition experiments indicated that the antiviral efficacy could be optimized when artesunate was applied as fractional doses consecutively added post-infection. Artesunate showed a clearly higher anti-cytomegaloviral activity than its parental drug artemisinin (approximately 10-fold) or other artesunate-related compounds. Mean IC 50 values of artesunate for a variety of standard therapy-resistant virus mutants were within a 2-fold range compared to wild-type virus. Furthermore, a synergistic effect was identified when artesunate was combined with the mechanistically distinct antiviral compound maribavir. These findings point to unique antiviral properties of artesunate which may offer an advantage over standard antiviral therapy particularly in cases of drug resistance.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalAntiviral Research
Volume92
Issue number2
DOIs
StatePublished - Nov 2011

Keywords

  • Antiviral activity of artesunate
  • Artesunate-related drugs
  • Human cytomegalovirus
  • Synergistic effect
  • Therapy-resistant virus mutants

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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