Chemical Diversity and In Vitro/In Silico Antiviral Activity of Extracts from Different Parts of Phyllanthus brasiliensis (Aubl.) Poir

Abstract

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.