Oral 4'-fluorouridine rescues mice from advanced lymphocytic choriomeningitis virus infection

Lymphocytic choriomeningitis virus (LCMV) can cause severe, life-threatening infection and disease in organ transplant recipients and other immunocompromised individuals. Additionally, significant developmental and neurological disabilities, vision impairments, and miscarriages can occur as a direct result of LCMV infection during pregnancy. Currently, there are no approved antiviral drugs to protect at-risk populations. Here, we report on the potent in vitro activity of the 4'-fluorouridine (4'-FlU) ribonucleoside analog against several strains of LCMV, with EC₉₀ values in the low micromolar range. In vivo, oral once-daily 4'-FlU treatments provided robust efficacy in mice challenged with LCMV when administered as late as 5 days post-infection. Our findings extend the broad-spectrum antiviral capacity of 4'-FlU and support the compound's further development for treating LCMV and other severe arenavirus infections.