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Updated: Dec 20, 2025
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Drug screening identifies gemcitabine inhibiting rotavirus through alteration of pyrimidine nucleotide synthesis
Sunrui Chen1, Yining Wang1, Pengfei Li1
1Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
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.
Insights
Gemcitabine, an anti-cancer drug, effectively inhibits rotavirus infection by interfering with pyrimidine biosynthesis. This finding supports repurposing gemcitabine for treating rotavirus, particularly in immunocompromised cancer patients.
Area of Science:
- Virology
- Oncology
- Pharmacology
Background:
- Rotavirus infections are typically self-limiting but can cause severe chronic disease in immunocompromised individuals.
- No approved antiviral medications currently exist for rotavirus infections.
- Immunocompromised patients, including transplant recipients and cancer patients, are at high risk for severe rotavirus disease.
Purpose of the Study:
- To screen for safe, broad-spectrum antiviral compounds against rotavirus.
- To identify potential therapeutic agents for rotavirus infections, especially in vulnerable populations.
- To investigate the mechanism of action of identified antiviral compounds.
Main Methods:
- Screening of a library of safe-in-man broad-spectrum antivirals.
- In vitro confirmation using 2D cell cultures and 3D human intestinal organoids.
- Testing against laboratory-adapted rotavirus strains and clinical isolates.
- Investigating the mechanism by assessing the effect of UTP or uridine supplementation.
Main Results:
- Gemcitabine, a chemotherapy drug, demonstrated potent inhibition of rotavirus infection.
- The anti-rotavirus activity of gemcitabine was confirmed in both cell culture models and organoids.
- Activity was observed against multiple rotavirus strains, including clinical isolates.
- Supplementation with UTP or uridine significantly reduced gemcitabine's antiviral effect, indicating a link to pyrimidine biosynthesis.
Conclusions:
- Gemcitabine shows significant potential for repositioning as a treatment for rotavirus infections.
- The mechanism of action involves the inhibition of the pyrimidine biosynthesis pathway.
- This discovery offers a promising therapeutic avenue for immunocompromised patients, especially cancer patients, suffering from rotavirus.
