Remdesivir inhibits the progression of experimental colitis stimulated by dextran sodium sulfate

Remdesivir, a broad-spectrum antiviral prodrug, has been investigated for its potential effects on inflammatory bowel disease (IBD). Using a mouse model with acute colitis induced by 3% dextran sulfate sodium (DSS), we administered remdesivir at doses of 12.5 and 25 mg/kg from day 1 to 7. Our research demonstrated that remdesivir treatment notably decreased disease activity scores and improved colon tissue damage under the microscope. It also boosted the levels of tight junction proteins such as occludin and claudin-1, while reducing the production of inflammatory cytokines like IL-1β, IL-6, and TNF-α, as well as the adhesion molecule ICAM-1. Further analysis showed that remdesivir significantly reduced the expression of inflammatory markers CD3, EMR, and MPO in the mice's colorectal tissues. Additionally, it was found to regulate the gut microbiota and restore bile acid levels. Remdesivir was also observed to stabilize AnxA5, modulating the NF-κB pathway and thereby reducing inflammation, which was confirmed by its ability to counteract the effects of Si-AnxA5 suppression in LPS-treated Caco-2 cells. These findings indicate that remdesivir may activate the AnxA5 signaling pathway, offering a new perspective for treating experimental colitis. This suggests that remdesivir could be a valuable candidate for further development and therapeutic refinement in the context of IBD.