Exploring the antiviral potential of justicidin B and four glycosylated lignans from Phyllanthus brasiliensis against Zika virus: A promising pharmacological approach.

BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus that in recent years has been associated with cases of severe neurological disorders, such as microcephaly in newborns and Guillain-Barré syndrome in adults. As there is no vaccine or treatment, the search for new therapeutic targets is of great relevance. In this sense, plants are extremely rich sources for the discovery of new bioactive compounds and the species Phyllanthus brasiliensis (native to the Amazon region) remains unexplored. PURPOSE: To investigate the potential antiviral activity of compounds isolated from P. brasiliensis leaves against ZIKV infection. METHODS: In vitro antiviral assays were performed with justicidin B (a lignan) and four glycosylated lignans (tuberculatin, phyllanthostatin A, 5-O-ß-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIKV in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quantify viral load. In addition, for justicidin B, tests were performed to investigate the mechanism of action (virucidal, adsorption, internalization, post-infection). RESULTS: The isolated compounds showed potent anti-ZIKV activities and high selectivity indexes. Moreover, justicidin B, tuberculatin, and phyllanthostatin A completely reduced the viral load in at least one of the concentrations evaluated. Among them, justicidin B stood out as the main active, and further investigation revealed that justicidin B exerts its antiviral effect during post-infection stages, resulting in a remarkable 99.9 % reduction in viral load when treatment was initiated 24 h after infection. CONCLUSION: Our findings suggest that justicidin B inhibits endosomal internalization and acidification, effectively interrupting the viral multiplication cycle. Therefore, the findings shed light on the promising potential of isolated compounds isolated from P. brasiliensis, especially justicidin B, which could contribute to the drug development and treatments for Zika virus infections.

Untargeted-based metabolomics analysis and in vitro/in silico antiviral activity of extracts from Phyllanthus brasiliensis (Aubl.) Poir.

INTRODUCTION: This study describes the molecular profile and the potential antiviral activity of extracts from Phyllanthus brasiliensis, a plant widely found in the Brazilian Amazon. The research aims to shed light on the potential use of this species as a natural antiviral agent. METHODS: The extracts were analysed using liquid chromatography-mass spectrometry (LC-MS) system, a potent analytical technique to discover drug candidates. In the meantime, in vitro antiviral assays were performed against Mayaro, Oropouche, Chikungunya, and Zika viruses. In addition, the antiviral activity of annotated compounds was predicted by in silico methods. RESULTS: Overall, 44 compounds were annotated in this study. The results revealed that P. brasiliensis has a high content of fatty acids, flavones, flavan-3-ols, and lignans. Furthermore, in vitro assays revealed potent antiviral activity against different arboviruses, especially lignan-rich extracts against Zika virus (ZIKV), as follows: methanolic extract from bark (MEB) [effective concentration for 50% of the cells (EC50 ) = 0.80 µg/mL, selectivity index (SI) = 377.59], methanolic extract from the leaf (MEL) (EC50 = 0.84 µg/mL, SI = 297.62), and hydroalcoholic extract from the leaf (HEL) (EC50 = 1.36 µg/mL, SI = 735.29). These results were supported by interesting in silico prediction, where tuberculatin (a lignan) showed a high antiviral activity score. CONCLUSIONS: Phyllanthus brasiliensis extracts contain metabolites that could be a new kick-off point for the discovery of candidates for antiviral drug development, with lignans becoming a promising trend for further virology research.