Anti-chikungunya Activity of a Cinnamic Acid Derivative: An In Vitro and In Silico Study

Chikungunya virus (CHIKV) is an arthropod-borne virus that causes debilitating joint pain and fever with limited treatment options. Cinnamic acid, known for its broad-spectrum biological activities, and its derivatives were evaluated for their potential antiviral effects against CHIKV. In vitro experiments assessed the cytotoxicity of cinnamic acid and its derivatives and their efficacy in inhibiting CHIKV under different treatment settings. Additionally, molecular docking of the effective compounds with CHIKV proteins was performed to determine the probable targets. The results indicated that the derivative CATD-3, a 3,6-(substituted phenyl)-(1,2,4) triazolo [3,4-b][1,3,4] thiadiazole compound, showed antiviral activity under post-infection treatment conditions in Vero CCL-81 cells. The dose-dependent studies revealed that the 50% inhibitory concentration (IC50) was 11.49 µM and the selectivity index of CATD-3 was 13.39. The antiviral activity of CATD-3 was also observed in HeLa cells. In-silico studies revealed that the CATD-3 binds multiple non-structural proteins (nsP) i.e., nsP1, nsP2, and nsP4 of the virus with good binding energies and forming strong interactions with conserved residues on nsP1 methyl transferase (Val 129, Tyr 130, Ala 131) and nsP2 helicase (Met 91, Met 289, and Thr 261) and critical residues of the nsP4 RdRp (Arg331 and Asp 350). The combined in vitro and in silico studies underscores the therapeutic potential of cinnamic acid derivative, CATD-3, as a promising antiviral candidate against CHIKV.