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5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2

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Title: 5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2
Authors: Uemura, Kentaro Browse this author
Nobori, Haruaki Browse this author
Sato, Akihik Browse this author
Sanaki, Takao Browse this author
Toba, Shinsuke Browse this author
Sasaki, Michihito Browse this author →KAKEN DB
Murai, Akiho Browse this author
Saito-Tarashima, Noriko Browse this author
Minakawa, Noriaki Browse this author
Orba, Yasuko Browse this author →KAKEN DB
Kariwa, Hiroaki Browse this author →KAKEN DB
Hall, William W. Browse this author
Kaiwara, Hirofum Browse this author
Matsuda, Akira Browse this author →KAKEN DB
Maenaka, Katsumi Browse this author →KAKEN DB
Issue Date: 22-Oct-2021
Publisher: Cell Press
Journal Title: iScience
Volume: 24
Issue: 10
Start Page: 103120
Publisher DOI: 10.1016/j.isci.2021.103120
Abstract: Newly emerging or re-emerging viral infections continue to cause significant morbidity and mortality every year worldwide, resulting in serious effects on both health and the global economy. Despite significant drug discovery research against dengue viruses (DENVs) and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), no fully effective and specific drugs directed against these viruses have been discovered. Here, we examined the anti-DENV activity of tubercidin derivatives from a compound library from Hokkaido University and demonstrated that 5-hydroxymethyltubercidin (HMTU, HUP1108) possessed both potent anti-flavivirus and anti-coronavirus activities at submicromolar levels without significant cytotoxicity. Furthermore, HMTU inhibited viral RNA replication and specifically inhibited replication at the late stages of the SARS-CoV-2 infection process. Finally, we demonstrated that HMTU 5'-triphosphate inhibited RNA extension catalyzed by the viral RNA-dependent RNA polymerase. Our findings suggest that HMTU has the potential of serving as a lead compound for the development of a broad spectrum of antiviral agents, including SARS-CoV-2.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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