A diarylamine derived from anthranilic acid inhibits ZIKV replication

Suely Silva1,2, Jacqueline Farinha Shimizu1,2, Débora Moraes de Oliveira1

  • 1Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlandia, Uberlândia, MG, Brazil.

Scientific Reports
|November 29, 2019
PubMed

Insights

A novel diarylamine compound (FAM E3) shows significant antiviral activity against Zika virus (ZIKV), reducing viral replication. This compound targets the ZIKV NS3 helicase, offering a potential new therapeutic avenue.

Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Zika virus (ZIKV), a mosquito-borne Flavivirus, poses a significant public health threat with no approved antiviral treatments.
  • Recent ZIKV outbreaks highlight the urgent need for effective therapeutic interventions.

Purpose of the Study:

  • To identify and characterize novel antiviral compounds against ZIKV.
  • To investigate the mechanism of action of diarylamine compounds, specifically FAM E3, against ZIKV.

Main Methods:

  • Antiviral screening of diarylamines derived from anthranilic acid (FAMs) against ZIKV.
  • In vitro assays to evaluate viral replication inhibition by FAM E3.
  • In silico analysis to predict potential drug targets.
  • In vitro biophysical assays (thermal stability, ATPase activity) to assess FAM E3 interaction with ZIKV NS3 helicase domain (NS3Hel).

Main Results:

  • A synthetic FAM, E3, demonstrated significant anti-ZIKV activity, reducing viral replication by up to 86%.
  • FAM E3 did not appear to act by intercalating into viral dsRNA or interacting with SP6 RNA polymerase.
  • In silico studies predicted FAM E3 binding to the ZIKV NS3 helicase.
  • In vitro experiments confirmed that FAM E3 binds to and stabilizes the ZIKV NS3 helicase domain (NS3Hel).

Conclusions:

  • Diarylamine FAM E3 exhibits potent antiviral activity against Zika virus.
  • The ZIKV NS3 helicase is identified as a potential molecular target for FAM E3.
  • FAM E3 represents a promising lead compound for developing new ZIKV antiviral therapies.