title: DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection.
abstract: Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lu
authors.forename: Kristy J
authors.initials: KJ
authors.lastname: Szretter
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jin
authors.forename: Laura M
authors.initials: LM
authors.lastname: Aschenbrenner
authors.forename: Alice
authors.initials: A
authors.lastname: Lee
authors.forename: Stephen
authors.initials: S
authors.lastname: Hawley
authors.forename: Do Hyong
authors.initials: DH
authors.lastname: Kim
authors.forename: Michael P
authors.initials: MP
authors.lastname: Malakhov
authors.forename: Mang
authors.initials: M
authors.lastname: Yu
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012794:Sialic Acids / Q000008:administration & dosage / Q000494:pharmacology; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; D014760:Viral Fusion Proteins; C525612:oplunofusp