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

Uemura, Kentaro; Nobori, Haruaki; Sato, Akihik; Sanaki, Takao; Toba, Shinsuke; Sasaki, Michihito; Murai, Akiho; Saito-Tarashima, Noriko; Minakawa, Noriaki; Orba, Yasuko; Kariwa, Hiroaki; Hall, William W.; Kaiwara, Hirofum; Matsuda, Akira; Maenaka, Katsumi

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

Uemura, Kentaro; Nobori, Haruaki; Sato, Akihik et al.

iScience, 2021, 24(10), 103120

Permalink : https://hdl.handle.net/2115/83593

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https://doi.org/10.1016/j.isci.2021.103120

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アクセス権	metadata only access
URI	https://hdl.handle.net/2115/83593
タイトル	5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2
著者	Uemura, Kentaro ; Nobori, Haruaki ; Sato, Akihik ; Sanaki, Takao ; Toba, Shinsuke ; Sasaki, Michihito ; Murai, Akiho ; Saito-Tarashima, Noriko ; Minakawa, Noriaki ; Orba, Yasuko ; Kariwa, Hiroaki ; Hall, William W. ; Kaiwara, Hirofum ; Matsuda, Akira ; Maenaka, Katsumi
著者名 Uemura, Kentaro
著者名 Nobori, Haruaki
著者名 Sato, Akihik
著者名 Sanaki, Takao
著者名 Toba, Shinsuke
e-Rad_Researcher 70609403 著者名 Sasaki, Michihito
著者名 Murai, Akiho
著者名 Saito-Tarashima, Noriko
著者名 Minakawa, Noriaki
e-Rad_Researcher 60507169 著者名 Orba, Yasuko
e-Rad_Researcher 70224714 著者名 Kariwa, Hiroaki
著者名 Hall, William W.
著者名 Kaiwara, Hirofum
e-Rad_Researcher 90157313 著者名 Matsuda, Akira
e-Rad_Researcher 10322752 著者名 Maenaka, Katsumi
言語	英語
発行日	2021-10-22
出版者	Cell Press
収録物名	iScience
巻(号)	24(10)
ページ	103120
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
EISSN	2589-0042
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.isci.2021.103120