Introduction: Plants of the genus Phyllanthus (Euphorbiaceae), the “stone breaker” has long been used in folk medicine to treat hepatitis B, an important viral disease. In this regard some species of this genus were tested against viruses as Herpes simplex virus type 1 (HSV-1), COVID and Hepatitis C virus (HCV), showing expressive inhibition in some of them, attracting attention to the genus and to its chemical constituents. Although P. brasiliensis has no traditional use as an antiviral plant, these findings urge us to consider whether P. brasiliensis, plant widely distributed in the Brazilian Amazon and its compounds have antiviral activity against Vero cell lines infected with Mayaro, Oropouche, Chikungunya, and Zika viruses. Objectives: Thus, herein we describe a study of extracts' chemical diversity, antiviral activity, and specialized metabolites detected in different parts of the Phyllanthus brasiliensis (Aubl.) Poir., Methods: In this context, liquid chromatography-mass spectrometry is a crucial analytical method to reveal the identity of many drug candidates from extracts from medicinal plants used to treat diseases, including for instance infections by viruses. Results: As result, 44 compounds were annotated by mass spectrometry-based molecular networking approach. Along, the extracts were tested against Vero cell lines infected with Mayaro, Oropouche, Chikungunya, and Zika viruses. Overall, the results revealed that this species is high in fatty acids, flavones, flavan-3-ols, and lignans. Among them, especially lignans are known to have promising antiviral properties. In this context, in vitro assays revealed potent antiviral activity against different viruses, especially lignan-rich extracts MEB (EC50 = 0.80 µg.mL− 1, SI = 377.59), MEL (EC50 = 0.84 µg.mL− 1, SI = 297.62), and HEL (EC50 = 1.36 µg.mL− 1, SI = 735.29) against Zika virus (ZIKV). Conclusions: The potential of lignans was also supported by in silico antiviral prediction, and Tuberculatin (a lignan) stood out with high activity score and as a strong candidate from MEL extract. Therefore, authors believe that P. brasiliensis extracts contain metabolites that could be a new kick-off point with candidates for antiviral drug development, with lignans becoming a promising trend for further virology research.

IntroductionThis 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.MethodsThe 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.ResultsOverall, 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.ConclusionsPhyllanthus 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.

Deguelia nitidula (Benth.) A.M.G.Azevedo & R.A.Camargo (Fabaceae) is an herbaceous plant distributed in the Brazilian Amazon, and it is called “raiz do sol” (sun roots). On Marajó Island, quilombola communities use its prepared roots to treat skin diseases commonly caused by fungi, viruses, and bacteria. Thus, in this study, the extract, and its fractions from D. nitidula roots were used to perform in vitro cytotoxic and antibacterial assays against Staphylococcus aureus strains. Thereafter, liquid chromatography–mass spectrometry (LC–MS) was used for the metabolite annotation process. The ethanolic extract of D. nitidula roots show significant bactericidal activity against S. aureus with IC50 82 μg.mL−1 and a selectivity index (SI) of 21.35. Furthermore, the SREFr2 and SREFr3 fractions show a potent bactericidal activity, i.e., MIC of 46.8 μg.mL−1 for both, and MBC of 375 and 93.7 μg.mL−1, respectively. As showcased, SREFr3 shows safe and effective antibacterial activity mainly in respect to the excellent selectivity index (SI = 82.06). On the other hand, SREFr2 shows low selectivity (SI = 6.8), which characterizes it as not safe for therapeutic use. Otherwise, due to a limited amount of reference MS2 spectra in public libraries, up to now, it was not possible to perform a complete metabolite annotation. Despite that, our antibacterial results for SREFr3 and correlated substructures of amino acid derivatives show that the roots of D. nitidula are a natural source of specialized metabolites, which can be isolated in the future, and then used as a support for further bio-guided research, as well as natural drug development.