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<p>Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures. Importantly, the cocktail did not alter glucose and insulin levels in the culture medium of pancreatic β-cells and preserved the contraction rhythm of infected heart organoids. These findings highlight a promising drug cocktail for further preclinical studies and clinical trials targeting a broad range of enterovirus-mediated diseases.</p>

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Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月23日

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  • Erlend Ravlo,
  • Aleksandr Ianevski,
  • Jørn-Ove Schjølberg,
  • Vanessa Solvang,
  • Rabina Dumaru,
  • Hilde Lysvand,
  • Jacqueline Hankinson,
  • Markus Vähä-Koskela,
  • Sanna Vainionpää,
  • Anni Varhe,
  • Hanna Seppänen,
  • Teemu Smura,
  • Xin Wang,
  • Yining Wang,
  • Pengfei Li,
  • Qiuwei Pan,
  • Knut Dahl-Jorgensen,
  • Lars Krogvold,
  • Oleksandr Kamyshnyi,
  • Hans-Johnny Schjelderup Nilsen,
  • Inger Johanne Haugen,
  • Erling Høyer,
  • Jan Egil Afset,
  • Valentyn Oksenych,
  • Angel S. Galabov,
  • Adelina Stoyanova,
  • Vivian Lam,
  • Barbara van Loon,
  • Valeria Lulla,
  • Magnar Bjørås,
  • Denis E. Kainov

摘要

Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures. Importantly, the cocktail did not alter glucose and insulin levels in the culture medium of pancreatic β-cells and preserved the contraction rhythm of infected heart organoids. These findings highlight a promising drug cocktail for further preclinical studies and clinical trials targeting a broad range of enterovirus-mediated diseases.