Although rotavirus infection is usually acute and self-limiting, it can cause chronic infection with severe diseases in immunocompromised patients, including organ transplantation recipients and cancer patients irrespective of pediatric or adult patients. Since no approved medication against rotavirus infection is available, this study screened a library of safe-in-man broad-spectrum antivirals. We identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of rotavirus infection. We confirmed this effect in 2D cell cultures and 3D cultured human intestinal organoids with both laboratory-adapted rotavirus strains and five clinical isolates. Supplementation of UTP or uridine largely abolished the anti-rotavirus activity of gemcitabine, suggesting its function through inhibition of pyrimidine biosynthesis pathway. Our results support repositioning of gemcitabine for treating rotavirus infection, especially for infected cancer patients.

Additional Metadata
Keywords Broad-spectrum antiviral agents, Gemcitabine, Human intestinal organoids, Pyrimidine biosynthesis pathway, Rotavirus
Persistent URL dx.doi.org/10.1016/j.antiviral.2020.104823, hdl.handle.net/1765/127922
Journal Antiviral Research
Organisation Department of Gastroenterology & Hepatology
Citation
Chen, S, Wang, Y. (Yining), Li, P. (Pengfei), Yin, Y, Bijvelds, M.J.C, de Jonge, H.R, … Pan, Q. (2020). Drug screening identifies gemcitabine inhibiting rotavirus through alteration of pyrimidine nucleotide synthesis pathway. Antiviral Research, 180. doi:10.1016/j.antiviral.2020.104823