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Updated: May 2, 2026

Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses
09:07

Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses

Published on: January 20, 2017

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A novel C-3-substituted oleanolic acid benzyl amide derivative exhibits therapeutic potential against influenza A by

Kunyu Lu1, Jianfu He1, Chongjun Hong2

  • 1Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Acta Pharmaceutica Sinica. B
|September 2, 2025
PubMed

Insights

A novel compound, A5, effectively inhibits influenza A virus (IAV) replication by targeting the viral RNA polymerase. This potent antiviral agent shows broad-spectrum activity, including against drug-resistant strains, and enhances oseltamivir efficacy.

Area of Science:

  • Virology
  • Medicinal Chemistry
  • Immunology

Background:

  • Influenza A virus (IAV) poses a pandemic threat due to its contagiousness and emerging drug resistance.
  • The viral RNA polymerase is a critical target for developing anti-IAV therapeutics.

Purpose of the Study:

  • To identify and characterize novel inhibitors of IAV replication.
  • To evaluate the efficacy of a new compound, A5, against IAV, including drug-resistant strains.

Main Methods:

  • Biochemical assays to measure inhibition of PAC-PB1N polymerase subunit interaction.
  • Antiviral assays against laboratory and clinical IAV strains.
  • In vitro and in vivo efficacy studies in a murine model.
  • Analysis of immune responses, including TLR4 activation and cytokine production.

Main Results:

  • Compound A5 potently inhibited PAC-PB1N interaction (IC50 = 0.96 μmol/L).
  • A5 demonstrated broad-spectrum antiviral activity (EC50 = 0.60–1.83 μmol/L) against diverse IAV strains, including multidrug-resistant ones.
  • A5 showed synergistic effects with oseltamivir and significantly reduced viral load and mortality in mice.
  • A5 modulated immune responses by inhibiting TLR4 activation and reducing inflammation.

Conclusions:

  • A5 is a novel, potent inhibitor targeting the IAV RNA polymerase.
  • A5 exhibits broad-spectrum and synergistic antiviral activity, offering a promising therapeutic candidate.
  • A5 demonstrates immunomodulatory effects, potentially mitigating IAV-induced pathology.
Keywords:
Drug-resistant strainsInflammationInfluenza A virusOleanolic acid amide derivativesPentacyclic triterpenoidsProtein–protein interactionRNA polymeraseToll-like receptor 4

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