Zhang Rui, Feng Cui, Luo Dandan, Zhao Ruibo, Kannan Perumal Ramesh, Yin Yuebang, Iqbal Muhammad Zubair, Hu Yeting, Kong Xiangdong
Institute for Smart Biomedical Materials, School of Materials Science & Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Pharmaceuticals (Basel). 2023 Sep 11;16(9):1279. doi: 10.3390/ph16091279.
Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research.
轮状病毒是导致5岁以下儿童严重腹泻的主要病原体之一，主要感染小肠的肠上皮细胞。目前，针对轮状病毒的口服补液和抗病毒治疗尚无特效药物。然而，盐酸二甲双胍作为一种具有抗病毒特性的药物，因其在小肠中蓄积并调节肠道微生物群而显示出前景。因此，我们提出了一个假设，即盐酸二甲双胍可以抑制肠道中的轮状病毒复制。为了验证盐酸二甲双胍的抗轮状病毒作用，我们使用了从体外细胞和类器官到体内小肠等不同模型进行感染实验。研究结果表明，0.5 mM盐酸二甲双胍浓度可显著抑制Caco-2细胞、小肠类器官和乳鼠模型中轮状病毒mRNA和蛋白质的表达。轮状病毒感染会导致明显的病理变化，但观察到用二甲双胍治疗可减轻治疗组中轮状病毒感染引起的病变。我们的研究证实盐酸二甲双胍可以抑制轮状病毒复制，同时也肯定了类器官作为体外研究病毒模型的可靠性。
