2. Academic Validation
  3. 5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2

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

  • iScience. 2021 Oct 22;24(10):103120. doi: 10.1016/j.isci.2021.103120.
Kentaro Uemura 1 2 3,  Haruaki Nobori 1,  Akihiko Sato 1 2,  Takao Sanaki 1 2,  Shinsuke Toba 1 2,  Michihito Sasaki 2,  Akiho Murai 4,  Noriko Saito-Tarashima 4,  Noriaki Minakawa 4,  Yasuko Orba 2 5,  Hiroaki Kariwa 6,  William W Hall 5 7 8,  Hirofumi Sawa 2 5 8 9,  Akira Matsuda 10,  Katsumi Maenaka 3 10 11
Affiliations

Affiliations

  • 1 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
  • 2 Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  • 3 Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  • 4 Graduate School of Pharmaceutical Science, Tokushima University, Tokushima, Japan.
  • 5 International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  • 6 Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • 7 National Virus Reference Laboratory, School of Medicine, University College of Dublin, Ireland.
  • 8 Global Virus Network, Baltimore, MD, USA.
  • 9 One Health Research Center, Hokkaido University, Sapporo, Japan.
  • 10 Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  • 11 Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan.
PMID: 34541466 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 coronavirus-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.

Keywords

Drugs; Microbiology; Viral microbiology.

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