Combination of benzo[a]phenothiazines with acyclovir against herpes simplex virus

Ilona Mucsi, Joseph Molnár, Noboru Motohashi

Research output: Contribution to journalArticle

16 Citations (Scopus)


The combined antiviral effects of some benzo[a]phenothiazines and 9-[2-hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H-benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used to interpret the drug interaction and a synergistic effect was found with a combination of ACV and benzo[a]phenothiazines. The effect of simultaneous application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain during serial passages was also investigated. The combinations of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a low concentration using serial passages of a plaque-purified ACV sensitive HSV-2 strain, reduced the infective virus population. A similar effect was also found on the activity of other benzo[a]phenothiazine derivatives. When the two most effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2 strain during consecutive passages, the infective virus titres were decreased, but their effect was only moderate. These results suggest that a combination of some benzo[a]phenothiazines with ACV might enhance their antiviral activity probably by reduction of the mutagenic rate in the virus populations.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Issue number1
Publication statusPublished - Aug 14 2001


  • ACV
  • Benzo[a]phenothiazines
  • Combination
  • Herpes simplex virus
  • Synergism

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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