VV261

VV261 is an orally active prodrug of 4'-fluorouridine. VV261 inhibits viral RNA-dependent RNA polymerase. VV261 exhibits antiviral activity against CCHFV, SFTSV and LCMV. VV261 can be used in research related to viral infections^[1][2].
In Vitro, VV261 (up to 200 µM) potently inhibits CCHFV infection in HUVEC, with an EC₅₀ of 2.72 µM. It exhibits extremely low cytotoxicity, with a selectivity index greater than 73.53^[1]. VV261 (2-50 µM) inhibits the activity of CCHFV RdRp in BSR-T7/5 cells in a dose-dependent manner^[1]. VV261 (48 h) potently inhibits SFTSV replication in Vero-ATCC cells, with an EC₅₀ of 0.89 μM^[2]. VV261 (48 h) potently inhibits LCMV replication in A549 cells, with an EC₅₀ of 0.15 μM^[2].
In Vivo, VV261 (1-10 mg/kg; p.o.; once daily; for 6 consecutive days) inhibits viral replication in a lethal CCHFV mouse model^[1]. VV261 (2.5-10 mg/kg; p.o.; once daily; for 7 consecutive days) exhibits dose-dependent anti-SFTSV efficacy in IFNAR1^tm1Agt mice^[2]. VV261 (1-5 mg/kg; p.o.; once daily; for 7 consecutive days) exhibits dose-dependent anti-LCMV efficacy in C57BL/6-Prf1^tm1Sdz/J mice^[2].

References:
[1]. Wang X, et al. Oral VV261 administration protects mice from lethal Crimean-Congo hemorrhagic fever virus challenge. J Virol. 2025 Dec 23;99(12):e0158325.
[2]. Cheng Y, et al. Design and Development of a Novel Oral 4'-Fluorouridine Double Prodrug VV261 against SFTSV. J Med Chem. 2025;68(9):9811-9826.