Arboviruses such as chikungunya virus (CHIKV), Zika virus (ZIKV), and Mayaro virus (MAYV) represent significant global health challenges due to the lack of effective antiviral therapies. Quinoline-based compounds have emerged as promising scaffolds for antiviral drug development. In this study, five 4-amino-7-chloroquinoline derivatives were synthesized and evaluated for their in vitro antiviral activity against CHIKV, ZIKV, and MAYV in Vero cells. Cytotoxicity and antiviral effects were assessed using a tetrazolium-based assay, followed by complementary analyses including cytopathic effect inhibition, virucidal assay, and viral load quantification by RT-qPCR. Among the tested compounds, derivative 6 demonstrated the most pronounced anti-CHIKV activity, with a low micromolar effective concentration and moderate selectivity index. This compound significantly reduced viral replication, preserved cell monolayer integrity, and decreased viral titers, achieving substantial viral load reduction confirmed by RT-qPCR. No virucidal activity was observed. In contrast, compound 6 inhibited the virus-induced cytopathic effect when administered after viral adsorption, suggesting that its antiviral activity is unlikely to result from interference with viral attachment or adsorption but rather from inhibition of a post-adsorption stage of the viral replication cycle. Overall, these findings highlight 4-amino-7-chloroquinoline derivatives as a promising class of antiviral agents and identify compound 6 as a potential lead candidate for further development against CHIKV.
A. C. C. Reis, Camila Portruneli, Lívia da Cunha Agostini et al.· Current Microbiology· 0 citations
This study evaluated a panel of structurally diverse flavonoids, including monomeric, dimeric, and oligomeric compounds, to investigate the influence of structural complexity on antiviral activity against Chikungunya (CHIKV) and Mayaro (MAYV) viruses. CHIKV and MAYV, which are both members of the genus Alphavirus, represent a growing public health concern in Brazil. This is owing to rising arboviral infections and the potential for cotransmission by shared urban vectors. Effective control requires integrated strategies, including antivirals. Therefore, this study evaluated the cytotoxicity, antiviral activity, and in silico pharmacokinetic/toxicological profiles of nine structurally diverse compounds. Accordingly, procyanidins A2 (PA2), C1 (PC1), and genistein (GNT) displayed the most promising antiviral activity against CHIKV. Moreover, these compounds exhibited selectivity index (SI) values of 5.9, 10.4, and 2.6, with half maximal effective concentrations of 56.7, 50.2, and 64.4 μM, respectively. Furthermore, for the anti-MAYV activity, PA2 and PC1 exhibited SI values of 4.1 and 61, with EC50 values of 81.7 and 8.8 μM, respectively. In addition, GNT induced a 5-log reduction of CHIKV replication, whereas PC1 caused a 4-log reduction of MAYV replication. In virucidal assays, PA2 and PC1 nearly abolished (∼100%) CHIKV infectivity and reduced MAYV infectivity by approximately 80%.In silico analysis indicated that GNT had favorable pharmacokinetics and high toxicological safety, whereas PC1 demonstrated strong safety despite limited oral bioavailability. These results identify PC1 as the most promising candidate for future preclinical development, whereas GNT and PA2 should be considered lead compounds for further optimization strategies aimed at improving selectivity and safety profiles.
Delaine Meireles Gouvêa, Maria Cecília Muniz de Souza Brand, Millena Alves Máximo Vaz et al.· ACS Omega· 0 citations
