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Prophylaxis of ferrets with nitazoxanide and oseltamivir combinations is more effective at reducing the impact of influenza a virus infection compared to oseltamivir monotherapy.

Abstract
Combination therapy is an alternative approach to reduce viral shedding and improve clinical outcomes following influenza virus infections. In this study we used oseltamivir (OST), a neuraminidase inhibitor and nitazoxanide (NTZ), a host directed drug, and found in vitro that the combination of these two antivirals have a synergistic relationship. Using the ferret model of (A/Perth/265/2009, (H1N1)pdm09), virus infections, we found that the combination of NTZ and OST was more effective than either NTZ or OST independently in preventing infection and reducing duration of viral shedding. However, these benefits were only seen if treatment was administered prophylactically, as opposed to therapeutically. We also found that if prophylactically treated ferrets that had detectable virus in the upper respiratory tract, no virus was detected in the lower respiratory tract. This benefit was not observed with NTZ or OST alone. The combination of NTZ and OST enhances the antiviral effect of OST, which is the standard of care in most settings.
AuthorsEdin J Mifsud, Danielle Tilmanis, Ding Yuan Oh, Celeste Ming-Kay Tai, Jean-Francois Rossignol, Aeron C Hurt
JournalAntiviral research (Antiviral Res) Vol. 176 Pg. 104751 (04 2020) ISSN: 1872-9096 [Electronic] Netherlands
PMID32088248 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020. Published by Elsevier B.V.
Chemical References
  • Antiviral Agents
  • Drug Combinations
  • Nitro Compounds
  • Thiazoles
  • Oseltamivir
  • nitazoxanide
Topics
  • Administration, Oral
  • Animals
  • Antiviral Agents (administration & dosage)
  • Chemoprevention
  • Dogs
  • Drug Combinations
  • Drug Resistance, Viral
  • Female
  • Ferrets (virology)
  • Influenza A Virus, H1N1 Subtype (drug effects)
  • Lung (virology)
  • Madin Darby Canine Kidney Cells
  • Male
  • Nitro Compounds
  • Orthomyxoviridae Infections (prevention & control)
  • Oseltamivir (administration & dosage)
  • Thiazoles (administration & dosage)
  • Virus Shedding (drug effects)

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