Abstract
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.
Highlights
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
Specific and effective antiviral treatment is urgently needed for these special populations who are infected with rotavirus, but there are no FDA-approved medications available against rotavirus infection
We screened a library of safe-in-man broad-spectrum antiviral agents (BSAAs, https://drugvirus. info) (Andersen et al, 2020; Ianevski et al, 2018) on rotavirus infection in experimental models
Summary
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. Given that only the specific population with rotavirus infection require antiviral treatment, the pharmaceutical industry will likely not develop new anti-rotavirus drugs. We first screened 94 BSAAs in human intestinal Caco2 cell line infected with simian rotavirus SA11 strain (Table S1). We tested a series of gemcitabine concentrations (0.01–10 μM) in the Caco2 cell model to assess both antiviral and cytotoxic effects.
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