@article{1ef24bc903f041bf86322449bb2327d6,
title = "Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus",
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.",
keywords = "Antagonism, Cytomegalovirus, Ganciclovir, Maribavir, Sirolimus, Synergism",
author = "Sunwen Chou and Ercolani, {Ronald J.} and Katayoun Derakhchan",
note = "Funding Information: The authors thank Dr. Galen Carey (Shire, Cambridge, MA) and Dr. David Ehmann (Shire, Cambridge, MA) for their review and comments. This work was supported by a Shire-U.S. Department of Veterans Affairs (VA) Cooperative Research and Development Agreement ( CRADA ) and National Institutes of Health (NIH grant AI116635 ). VA provided research resources and facilities. KD is an employee of Shire. SC is principal investigator on an unrelated Merck-VA CRADA. Role of funding sources: All CRADA payments are to the institution for research costs; no portion is income for the principal investigator. Study design was a Shire-VA collaboration, except that maribavir-rapamycin combination assays were solely NIH-funded research. Collection, analysis and interpretation of data were performed by VA staff. The manuscript was written by the first author with review and comment by other authors and Shire staff. The contents are not a statement of views of any agency of the United States Government. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",
year = "2018",
month = sep,
doi = "10.1016/j.antiviral.2018.07.013",
language = "English (US)",
volume = "157",
pages = "128--133",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
}