| 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 |
| URI: | http://hdl.handle.net/2115/83593 |
| 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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