Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel.

Zika virus (ZIKV) diagnosis is currently performed through an invasive, painful, and costly procedure using molecular biology. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for ZIKV diagnosis is of great relevance. It is critical to prepare a global strategy for the next ZIKV outbreak given its devastating consequences, particularly in pregnant women. Attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy has been used to discriminate systemic diseases using saliva; however, the salivary diagnostic application in viral diseases is unknown. To test this hypothesis, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with ZIKV (50 µL,105 FFU, n = 7) or vehicle (50 µL, n = 8). Saliva samples were collected on day three (due to the peak of viremia) and the spleen was also harvested. Changes in the salivary spectral profile were analyzed by Student’s t test (p < 0.05), multivariate analysis, and the diagnostic capacity by ROC curve. ZIKV infection was confirmed by real-time PCR of the spleen sample. The infrared spectroscopy coupled with univariate analysis suggested the vibrational mode at 1547 cm−1 as a potential candidate to discriminate ZIKV and control salivary samples. Three PCs explained 93.2% of the cumulative variance in PCA analysis and the spectrochemical analysis with LDA achieved an accuracy of 93.3%, with a specificity of 87.5% and sensitivity of 100%. The PCA-SVM analysis showed 100% discrimination between both classes. Our results suggest that ATR-FTIR applied to saliva might have high accuracy in ZIKV diagnosis with potential as a non-invasive and cost-effective diagnostic tool.