Effectiveness of 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds against chikungunya virus.

Aim: Chikungunya fever (CHIKF) caused by the chikungunya virus (CHIKV) is characterized by the presence of long-term polyarthralgia in a minor proportion of the infected patients. Currently, there are no FDA-approved antivirals available. This study evaluated the anti-CHIKV potential of 16 synthetic 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds and elucidated their probable mechanisms of action.

Methods: Anti-CHIKV activity of 16 compounds were investigated in Vero CCL-81 cells using focus forming unit assay (FFU). Dose-dependent and time-dependent antiviral assays were performed for the effective compounds. Molecular docking was performed to find out their interactions with viral proteins.

Results: Five compounds showed promising anti-CHIKV activity by reducing viral titer with >1 log₁₀ FFU/ml. Dose-dependent studies revealed that the compound 3 g was more effective in reducing the virus titer with a half-maximal inhibitory concentration (IC₅₀) of 0.4315 μM and a selectivity index of 35.99. Docking analyses revealed that all the compounds mainly interact with the non-structural proteins of CHIKV.

Conclusions: These findings demonstrate the in vitro anti-CHIKV activity of these compounds, and their possible mode of action via interference with early stages of infection and replication processes. This study warrants further preclinical and clinical evaluation to establish their safety and efficacy as novel anti-CHIKV therapeutics.