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

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  • Additional Information
    • Source:
      Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE
    • Publication Information:
      Publication: Stuttgart : Urban & Fischer Verlag
      Original Publication: Stuttgart ; New York : G. Fischer, c1994-
    • Subject Terms:
      Zika Virus* ; Zika Virus Infection*/drug therapy ; Phyllanthus* ; Lignans*/pharmacology ; Lignans*/therapeutic use ; Dioxolanes* ; Glycosides* ; Naphthalenes*; Infant, Newborn ; Animals ; Humans ; Chlorocebus aethiops ; Vero Cells ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Virus Replication
    • Abstract:
      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-β-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.
      Competing Interests: Declaration of Competing Interest The authors declare that is no conflict of interest.
      (Copyright © 2023 Elsevier GmbH. All rights reserved.)
    • Contributed Indexing:
      Keywords: Justicidin B; Phyllanthostatin A; Tuberculatin; Zika, antiviral; “Quebra-Pedra”
    • Accession Number:
      119767-19-0 (phyllanthostatin A)
      0 (justicidins)
      0 (Antiviral Agents)
      0 (Lignans)
      0 (Dioxolanes)
      0 (Glycosides)
      0 (Naphthalenes)
    • Publication Date:
      Date Created: 20231112 Date Completed: 20240117 Latest Revision: 20240117
    • Publication Date:
      20240117
    • Accession Number:
      10.1016/j.phymed.2023.155197
    • Accession Number:
      37952409