Chlorinated biscoumarins inhibit chikungunya virus replication in cell-based and animal models.

ABSTRACT: Biscoumarin derivatives were evaluated for antiviral activity against chikungunya virus (CHIKV), a re-emerging mosquito-borne alphavirus with no approved treatment. Compounds 3 and 4 demonstrated potent in vitro antiviral efficacy, with EC₅₀ values of 2.85 ± 0.42 µM and 3.08 ± 0.45 µM (SI > 20) for compound 3 in Vero and HEK293 cells, respectively. Compound 4 showed comparable potency in Vero cells but was less effective in HEK293 cells. Time-of-addition and replicon assays suggested that both compounds act at a post-entry step, likely inhibiting viral RNA replication. In vivo, a single oral dose of 250 mg/kg was well tolerated in mice and rats, with no signs of acute hepatorenal toxicity and favourable pharmacokinetic profiles. Compound 3 & 4 significantly reduced tissue vir

SUBMITTER: Orji CN 

PROVIDER: S-EPMC12305873 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature