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Peer-reviewedCC BY-NC-NDVirus research

In vivo antiviral efficacy and safety of 5-hydroxymethyltubercidin against DENV2 and SARS-CoV-2

  • Kentaro Uemura1
  • Shinsuke Toba2
  • Shinji Kusakabe2
  • Michihito Sasaki2
  • Yasuko Orba2
  • Naoyoshi Maeda1
  • Mayumi Ishii3
  • Kayoko Kanamitsu3
  • Hirofumi Sawa2
  • Akira Matsuda1
  • Akihiko Sato2
  • Katsumi Maenaka1
  1. 1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
  2. 2International Institute for Zoonosis Control (IIZC), Hokkaido University, Sapporo, Japan
  3. 3Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
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Abstract

Several newly emerging and re-emerging viral infections significantly affect human health and the global economy each year. As many of these viruses lack treatment options other than symptomatic management, the development of effective preventive and therapeutic measures is urgently needed. We previously identified 5-hydroxymethyltubercidin (HMTU) as a broad-spectrum antiviral ribonucleoside analog and demonstrated its in vitro potent antiviral activity against positive-sense single-stranded RNA viruses, including dengue virus (DENV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we evaluated the in vivo efficacy, pharmacokinetics, and safety of HMTU. Pharmacokinetic analysis revealed that effective concentrations of HMTU were maintained in the plasma and lung tissues of mice following intravenous and intramuscular administration. In a DENV2 infection model using AG129 mice, prophylactic administration of HMTU provided 100% protection against lethal infection. Similarly, in a SARS-CoV-2 infection model using BALB/c mice, HMTU significantly reduced viral titers in the lungs and improved the survival rates versus those in vehicle-treated mice. Furthermore, mutagenicity assessments using the Ames and HPRT tests demonstrated that HMTU did not exhibit mutagenic activity under the tested conditions. Our findings highlight HMTU as a broad-spectrum antiviral candidate potentially offering a promising therapeutic approach for dengue, COVID-19, and other infectious diseases caused by emerging orthoflaviviruses and coronaviruses.

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Cite

BibTeXRIS
BibTeX
@article{uemura2026vivo,
  title = {{In vivo antiviral efficacy and safety of 5-hydroxymethyltubercidin against DENV2 and SARS-CoV-2}},
  author = {Kentaro Uemura and Shinsuke Toba and Shinji Kusakabe and Michihito Sasaki and Yasuko Orba and Naoyoshi Maeda and Mayumi Ishii and Kayoko Kanamitsu and Hirofumi Sawa and Akira Matsuda and Akihiko Sato and Katsumi Maenaka},
  journal = {Virus research},
  year = {2026},
  month = oct,
  doi = {10.1016/j.virusres.2026.199817},
  url = {https://europepmc.org/article/PMC/PMC13718847},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - In vivo antiviral efficacy and safety of 5-hydroxymethyltubercidin against DENV2 and SARS-CoV-2
AU  - Kentaro Uemura
AU  - Shinsuke Toba
AU  - Shinji Kusakabe
AU  - Michihito Sasaki
AU  - Yasuko Orba
AU  - Naoyoshi Maeda
AU  - Mayumi Ishii
AU  - Kayoko Kanamitsu
AU  - Hirofumi Sawa
AU  - Akira Matsuda
AU  - Akihiko Sato
AU  - Katsumi Maenaka
PY  - 2026
DA  - 2026/10/13
JO  - Virus research
DO  - 10.1016/j.virusres.2026.199817
UR  - https://europepmc.org/article/PMC/PMC13718847
AB  - Several newly emerging and re-emerging viral infections significantly affect human health and the global economy each year. As many of these viruses lack treatment options other than symptomatic management, the development of effective preventive and therapeutic measures is urgently needed. We previously identified 5-hydroxymethyltubercidin (HMTU) as a broad-spectrum antiviral ribonucleoside analog and demonstrated its in vitro potent antiviral activity against positive-sense single-stranded RNA viruses, including dengue virus (DENV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we evaluated the in vivo efficacy, pharmacokinetics, and safety of HMTU. Pharmacokinetic analysis revealed that effective concentrations of HMTU were maintained in the plasma and lung tissues of mice following intravenous and intramuscular administration. In a DENV2 infection model using AG129 mice, prophylactic administration of HMTU provided 100% protection against lethal infection. Similarly, in a SARS-CoV-2 infection model using BALB/c mice, HMTU significantly reduced viral titers in the lungs and improved the survival rates versus those in vehicle-treated mice. Furthermore, mutagenicity assessments using the Ames and HPRT tests demonstrated that HMTU did not exhibit mutagenic activity under the tested conditions. Our findings highlight HMTU as a broad-spectrum antiviral candidate potentially offering a promising therapeutic approach for dengue, COVID-19, and other infectious diseases caused by emerging orthoflaviviruses and coronaviruses.
SN  - 0168-1702
SN  - 1872-7492
ER  -