In vitro study of the inhibitory potential of hydroxy-1,2,3-triazoles on the replication of ZIKA and chikungunya arboviruses

Abstract

Arboviruses, including Zika (ZIKV) and Chikungunya virus (CHIKV), replicate in both arthropods and vertebrates and are transmitted through mosquito, tick, and sandfly bites. The development of specific antiviral drugs and vaccines for these viruses is limited, highlighting the importance of investigating potential drug candidates. In this study, we examined the effects of hydroxy-triazole-based compounds on the in vitro replication of ZIKV and CHIKV. Hydroxy-1,2,3-triazoles were synthesized from 4-acyl-1,2,3-triazoles, previously prepared by the cycloaddition of enaminones and aryl azides, yielding good results. Cytotoxicity assessments using Vero cells showed low toxicity for the tested compounds, with a CC50 greater than 200 µM. Among these compounds, LSO150 and LSO163 demonstrated potent inhibitory effects against ZIKV, while LSO149, LSO151, LSO155, and LSO166 showed remarkable inhibitory effects on CHIKV. These molecules exhibited 99 % inhibition of viral replication at a concentration of 20 µM, with LSO163 and LSO149 particularly effective against ZIKV and CHIKV, respectively. The compounds maintained an inhibitory potential above 80 % when added to infected cells within 8 h after infection. Further investigation into the mechanism of action revealed that LSO163 had strong activity in viral adsorption, with a dose-dependent effect of over 90 % inhibition at a concentration of 20 µM. Additionally, when combined with suboptimal doses of Ribavirin (0.5 µM), the compound LSO149 showed a strong effect on CHIKV replication, inhibiting it by over 90 %. Our results suggest that LSO163 and LSO149 have high potential as drugs against ZIKV and CHIKV.

Keywords

• Arbovirus
• ZIKV
• CHIKV
• Antiviral
• Hydroxy-1,2,3-triazoles
• 1,3-dipolar cycloaddition