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Combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin Exert Synergistic Effects Against Influenza

Kuan Chien Tan1, Julia H Y Neo1, Thai Tran2

  • 1Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.

Pathogens (Basel, Switzerland)
|February 27, 2026
PubMed

Insights

This study shows that combining Favipiravir with Doxycycline, Azithromycin, or Ivermectin effectively inhibits influenza A virus replication. These combinations also reduce key pro-inflammatory cytokines, suggesting potential for severe influenza treatment.

Area of Science:

  • Virology and Infectious Diseases
  • Pharmacology and Drug Discovery
  • Immunology

Background:

  • Influenza A virus poses a significant global health threat, with severe infections linked to dangerous cytokine storms.
  • Existing antiviral treatments face challenges due to viral resistance and high mutation rates.
  • Repurposed drugs offer potential for novel combination therapies against influenza.

Purpose of the Study:

  • To evaluate the efficacy of Favipiravir combined with repurposed drugs against influenza A virus.
  • To assess the impact of these drug combinations on cytokine expression profiles.
  • To identify synergistic or additive effects for potential influenza treatment strategies.

Main Methods:

  • Tested combinations of Favipiravir with Doxycycline, Azithromycin, Ivermectin, Artesunate, and Andrographolide.
  • Measured inhibition of live influenza H3N2 clinical strain virus titers.
  • Analyzed relative mRNA expression of pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, IL-1β).

Main Results:

  • Favipiravir combined with Doxycycline, Azithromycin, or Ivermectin significantly inhibited virus titers by 4 log10.
  • Favipiravir-Doxycycline and Favipiravir-Azithromycin combinations reduced key pro-inflammatory cytokine mRNA expression.
  • Andrographolide monotherapy also achieved a 4 log10 reduction in virus titers.

Conclusions:

  • Specific drug combinations, particularly Favipiravir with Doxycycline or Azithromycin, demonstrate potent antiviral and immunomodulatory effects.
  • These combinations show promise for treating influenza, especially severe cases associated with cytokine storms.
  • Further research in human cell, tissue, and animal models is warranted to validate these findings.
Keywords:
andrographolideartesunateazithromycincombination therapycytokine expressiondoxycyclinedrug repurposingfavipiravirinfluenza virusivermectinsynergism

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