Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus

Sunwen Chou, Ronald J. Ercolani, Katayoun Derakhchan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The human cytomegalovirus (CMV) UL97 kinase inhibitor maribavir is in Phase III clinical trials as antiviral therapy, including use for infections refractory or resistant to standard therapy. To assess its activity in combination with approved and experimental CMV antivirals, and with the mTor inhibitor rapamycin (sirolimus), drug effects were tested by in vitro checkerboard assays and the data were analyzed using a three dimensional model based on an independent effects definition of additive interactions. Baseline virus and representative drug-resistant mutants were tested. According to the volume of synergy at 95% confidence, maribavir showed additive interactions with foscarnet, cidofovir, letermovir and GW275175X when tested against wild type and mutant viruses, strong antagonism with ganciclovir, and strong synergy with rapamycin, the latter suggesting a potentially useful therapeutic combination.

Original languageEnglish (US)
Pages (from-to)128-133
Number of pages6
JournalAntiviral Research
Volume157
DOIs
StatePublished - Sep 1 2018

Keywords

  • Antagonism
  • Cytomegalovirus
  • Ganciclovir
  • Maribavir
  • Sirolimus
  • Synergism

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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