title: The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model.
abstract: BACKGROUND
  Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo.
  
  
  RESULTS
  We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection.
  
  
  CONCLUSIONS
  A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Morokutti-Kurz
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Marielle
authors.initials: M
authors.lastname: König-Schuster
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Koller
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Graf
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Graf
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Norman
authors.initials: N
authors.lastname: Kirchoff
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Reutterer
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Jan-Marcus
authors.initials: JM
authors.lastname: Seifert
authors.affiliation: Laboratory of Tropical Veterinary Medicine, Veterinary University Vienna, Vienna, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Unger
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grassauer
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Prieschl-Grassauer
authors.affiliation: Marinomed Biotechnologie GmbH, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Nakowitsch
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002351:Carrageenan / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D016896:Treatment Outcome; D053243:Zanamivir / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D002351:Carrageenan; D053243:Zanamivir