The 2′-α-Fluoro,2′-β-Bromo uridine phosphoramidate prodrug (2-BFU) reduces dengue virus replication and attenuates infection-induced thrombocytopenia In Vivo

Dengue virus (DENV) infection remains a major global health concern, with clinical manifestations ranging from mild febrile illness to severe, life-threatening complications. In the absence of specific antiviral therapies, the development of novel treatment strategies is crucial. This study evaluates the in vivo antiviral efficacy of 2-BFU, a 2′-α-fluoro,2′-β-bromouridine monophosphate prodrug, in a murine model of DENV Serotype 2 (DENV-2) infection. Adult A129 mice were infected subcutaneously with DENV-2 and treated intraperitoneally with 2-BFU at 15 mg/kg, starting 12 h post-infection. Treatment with 2-BFU significantly reduced viral titers in plasma, spleen, and liver, demonstrating potent antiviral activity. Moreover, 2-BFU effectively attenuated DENV-2 -induced thrombocytopenia at 72- and 120-h post-infection. However, the treatment did not significantly affect the production of inflammatory mediators, nor did it prevent infection-associated weight loss or mortality. These findings suggest that 2-BFU holds promise as an antiviral candidate by lowering viral burden and ameliorating thrombocytopenia, although it may require adjunctive anti-inflammatory strategies to improve overall clinical outcomes. Further investigation is warranted to optimize its therapeutic potential for dengue.