NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir

NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir

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 vari...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2021-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-021-24509-7
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spelling doaj-ac367d8e92bf4e2bb684ff635f13452f2021-07-11T11:42:19ZengNature Publishing GroupNature Communications2041-17232021-07-011211910.1038/s41467-021-24509-7NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovirRina Nishii0Takanori Mizuno1Daniel Rehling2Colton Smith3Brandi L. Clark4Xujie Zhao5Scott A. Brown6Brandon Smart7Takaya Moriyama8Yuji Yamada9Tatsuo Ichinohe10Makoto Onizuka11Yoshiko Atsuta12Lei Yang13Wenjian Yang14Paul G. Thomas15Pål Stenmark16Motohiro Kato17Jun J. Yang18Department of Pharmaceutical Sciences, St. Jude Children’s Research HospitalChildren’s Cancer Center, National Center for Child Health and DevelopmentDepartment of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm UniversityDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalDepartment of Immunology, St. Jude Children’s Research HospitalDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalDepartment of Immunology, St. Jude Children’s Research HospitalDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalChildren’s Cancer Center, National Center for Child Health and DevelopmentResearch Institute for Radiation Biology and Medicine, Hiroshima UniversityTokai University School of MedicineJapanese Data Center for Hematopoietic Cell TransplantationDepartment of Chemical Biology & Therapeutics, St. Jude Children’s Research HospitalDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalDepartment of Immunology, St. Jude Children’s Research HospitalDepartment of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm UniversityChildren’s Cancer Center, National Center for Child Health and DevelopmentDepartment of Pharmaceutical Sciences, St. Jude Children’s Research HospitalNucleoside 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.https://doi.org/10.1038/s41467-021-24509-7
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
Nature Communications
author_facet 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
author_sort Rina Nishii
title NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
title_short NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
title_full NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
title_fullStr NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
title_full_unstemmed NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
title_sort nudt15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2021-07-01
description 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.
url https://doi.org/10.1038/s41467-021-24509-7
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