Nature Communications (Jul 2021)
NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
- Rina Nishii,
- Takanori Mizuno,
- Daniel Rehling,
- Colton Smith,
- Brandi L. Clark,
- Xujie Zhao,
- Scott A. Brown,
- Brandon Smart,
- Takaya Moriyama,
- Yuji Yamada,
- Tatsuo Ichinohe,
- Makoto Onizuka,
- Yoshiko Atsuta,
- Lei Yang,
- Wenjian Yang,
- Paul G. Thomas,
- Pål Stenmark,
- Motohiro Kato,
- Jun J. Yang
Affiliations
- Rina Nishii
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Takanori Mizuno
- Children’s Cancer Center, National Center for Child Health and Development
- Daniel Rehling
- Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University
- Colton Smith
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Brandi L. Clark
- Department of Immunology, St. Jude Children’s Research Hospital
- Xujie Zhao
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Scott A. Brown
- Department of Immunology, St. Jude Children’s Research Hospital
- Brandon Smart
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Takaya Moriyama
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Yuji Yamada
- Children’s Cancer Center, National Center for Child Health and Development
- Tatsuo Ichinohe
- Research Institute for Radiation Biology and Medicine, Hiroshima University
- Makoto Onizuka
- Tokai University School of Medicine
- Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation
- Lei Yang
- Department of Chemical Biology & Therapeutics, St. Jude Children’s Research Hospital
- Wenjian Yang
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Paul G. Thomas
- Department of Immunology, St. Jude Children’s Research Hospital
- Pål Stenmark
- Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University
- Motohiro Kato
- Children’s Cancer Center, National Center for Child Health and Development
- Jun J. Yang
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- DOI
- https://doi.org/10.1038/s41467-021-24509-7
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 9
Abstract
Nucleoside analogs (NNA), such as acyclovir (ACV) and ganciclovir (GCV), are widely used as anti-virals to treat herpes virus infection. Here, Nishii et al. show that diphosphatase NUDT15 hydrolyzes ACV and GCV, therewith reducing NNA activity in vitro and link NUDT15 variation to inter-patient variability in ACV and GCV therapeutic effects.
