2. Academic Validation
  3. 2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses

2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses

  • Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2304139120. doi: 10.1073/pnas.2304139120.
Kentaro Uemura 1 2 3 4,  Haruaki Nobori 2,  Akihiko Sato 2 3 5,  Shinsuke Toba 2 3,  Shinji Kusakabe 2 3,  Michihito Sasaki 3,  Koshiro Tabata 3,  Keita Matsuno 6 7 8,  Naoyoshi Maeda 9,  Shiori Ito 1,  Mayu Tanaka 1,  Yuki Anraku 1,  Shunsuke Kita 1,  Mayumi Ishii 10,  Kayoko Kanamitsu 10,  Yasuko Orba 3 8,  Yoshiharu Matsuura 4,  William W Hall 8 11 12,  Hirofumi Sawa 3 5 7 8 12,  Hiroshi Kida 13,  Akira Matsuda 9,  Katsumi Maenaka 1 5 9 14
Affiliations

Affiliations

  • 1 Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • 2 Drug Discovery and Disease Research Laboratory, Shionogi & Co. Ltd., Osaka 561-0825, Japan.
  • 3 Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • 4 Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan.
  • 5 Institute for Vaccine Research and Development, Hokkaido University, Sapporo 001-0021, Japan.
  • 6 Unit of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • 7 One Health Research Center, Hokkaido University, Sapporo 001-0020, Japan.
  • 8 International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • 9 Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • 10 Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, Tokyo 113-0033, Japan.
  • 11 National Virus Reference Laboratory, School of Medicine, University College of Dublin, Dublin D04, Ireland.
  • 12 Global Virus Network, Baltimore, MD 21201.
  • 13 Laboratory for Biologics Development, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • 14 Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo 060-0812, Japan.
PMID: 37831739 DOI: 10.1073/pnas.2304139120
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically Dengue Virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many Other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum Antiviral ribonucleoside analogue that exhibited Antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum Antiviral agent not only against DENV and SARS-CoV-2 but Other ssRNA+ viruses.

Keywords

RNA-dependent RNA polymerase; SARS-CoV-2; antiviral; dengue virus; positive-strand RNA viruses.

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