Ravlo Erlend, Ianevski Aleksandr, Schjølberg Jørn-Ove, Solvang Vanessa, Dumaru Rabina, Lysvand Hilde, Hankinson Jacqueline, Vähä-Koskela Markus, Vainionpää Sanna, Varhe Anni, Seppänen Hanna, Smura Teemu, Wang Xin, Wang Yining, Li Pengfei, Pan Qiuwei, Dahl-Jorgensen Knut, Krogvold Lars, Kamyshnyi Oleksandr, Nilsen Hans-Johnny Schjelderup, Haugen Inger Johanne, Høyer Erling, Afset Jan Egil, Oksenych Valentyn, Galabov Angel S, Stoyanova Adelina, Lam Vivian, van Loon Barbara, Lulla Valeria, Bjørås Magnar, Kainov Denis E
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, Trondheim, 7028, Norway.
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, 0372, Norway.
Cell Mol Life Sci. 2025 Jan 23;82(1):57. doi: 10.1007/s00018-025-05581-4.
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.
肠道病毒可感染人体多个器官，引发如脑膜炎、普通感冒、手足口病、心肌炎、胰腺炎、肝炎、小儿麻痹症、败血症和1型糖尿病等疾病。目前，尚无获批的肠道病毒感染治疗方法。在本研究中，我们确定了口服可用、对人体安全的普来可那立、AG7404和民得维的协同组合，该组合在无毒浓度下可有效抑制肠道病毒在人细胞和类器官培养物中的复制。重要的是，该混合物未改变胰腺β细胞培养基中的葡萄糖和胰岛素水平，并维持了受感染心脏类器官的收缩节律。这些发现凸显了一种有前景的药物混合物，可用于针对广泛的肠道病毒介导疾病的进一步临床前研究和临床试验。
