2. Academic Validation
  3. Identification of Co-29, a 5-cyano-2-thiacetyl aromatic pyrimidinone, as a potential inhibitor targeting the RdRp of norovirus

Identification of Co-29, a 5-cyano-2-thiacetyl aromatic pyrimidinone, as a potential inhibitor targeting the RdRp of norovirus

  • Virol J. 2025 Apr 4;22(1):93. doi: 10.1186/s12985-025-02687-w.
Xianglan Liu # 1,  Jiaming Hu # 1 2,  Jiarui Wu # 3,  Yiru Tian 1 4,  Jinbo Wang 3,  Chunyan Wu 1,  Qingfeng Chen 1,  Leonard Krall 1,  Yanping He 5,  Qun Lu 6
Affiliations

Affiliations

  • 1 Center for Life Sciences, School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, Yunnan University, Kunming, Yunnan, China.
  • 2 School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • 3 Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan Provincial Center for Research and Development of Natural Products, Ministry of Education, School of Pharmacy, Yunnan University, Kunming, Yunnan, China.
  • 4 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences& Peking Union Medical College, Kunming, Yunnan, China.
  • 5 Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan Provincial Center for Research and Development of Natural Products, Ministry of Education, School of Pharmacy, Yunnan University, Kunming, Yunnan, China. yphe@ynu.edu.cn.
  • 6 Center for Life Sciences, School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, Yunnan University, Kunming, Yunnan, China. qunlu@ynu.edu.cn.
  • # Contributed equally.
PMID: 40186285 DOI: 10.1186/s12985-025-02687-w
Abstract

Background: Human norovirus (HNV) is the predominant pathogen causing outbreaks of acute gastroenteritis globally. Despite significant efforts to combat norovirus infections, there is currently no FDA approved vaccine or Antiviral drug available. Consequently, the development of effective Antiviral agents is of critical importance.

Methods and results: In this study, a series of 41 5-cyano-2-thiacetyl aromatic pyrimidinone compounds were designed and synthesized. A cell viability-based screening for anti-murine norovirus (MNV) compounds was conducted, revealing that compound 29 (hereafter used as Co-29) exhibited Antiviral activity against MNV. Co-29 demonstrated effective inhibition of MNVCW3 RNA replication, exhibiting an EC50 of 58.22 μM. An RdRp enzyme activity assay indicated that Co-29 directly inhibits RdRp activity to both MNV and HNV. Molecular docking studies suggested that Co-29 interacts with the palm region of RdRp via hydrogen bonding with specific residues, which are conserved in RdRps across MNV and HNV norovirus variants.

Conclusions: In conclusion, our study suggests that the newly synthesized Co-29 may serve as a potential Antiviral candidate or lead compound for future studies.

Keywords

Anti-norovirus agent; Co-29; Norovirus; RdRp.

Figures
Products
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    Product Name
    Description
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    Research Area
  • HY-10468
    99.90%, HCV NS5B聚合酶抑制剂
    HCV
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