Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds

Abstract

Zika virus (ZIKV) is a mosquito-borne virus belonging to the <i>Flaviviridae</i> family and is responsible for an exanthematous disease and severe neurological manifestations, such as microcephaly and Guillain-Barré syndrome. ZIKV has a single strand positive-sense RNA genome that is translated into structural and non-structural (NS) proteins. Although it has become endemic in most parts of the tropical world, Zika still does not have a specific treatment. Thus, in this work we evaluate the cytotoxicity and antiviral activities of 14 hybrid compounds formed by 1<i>H</i>-1,2,3-triazole, naphthoquinone and phthalimide groups. Most compounds showed low cytotoxicity to epithelial cells, specially the <b>3b</b> compound. After screening with all compounds, <b>4b</b> was the most active against ZIKV in the post-infection test, obtaining a 50% inhibition concentration (IC₅₀) of 146.0 µM and SI of 2.3. There were no significant results for the pre-treatment test. According to the molecular docking compound, <b>4b</b> was suggested with significant binding affinity for the NS5 RdRp protein target, which was further corroborated by molecular dynamic simulation studies.