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-Barre 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 discover y 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 fou r glycosylated lignans (tuberculatin, phyllanthostati n A, 5-O-beta-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIK V in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quanti f y 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-ZIK V 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.