title: An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality.
abstract: Human infections caused by avian influenza A virus type subtype H7N9 have been associated with substantial morbidity and mortality. Emergence of virus variants carrying markers of decreased susceptibility to neuraminidase inhibitors was reported. Here we show that DAS181 (Fludase), an antiviral drug with sialidase activity, potently inhibited replication of wild-type influenza A(H7N9) and its oseltamivir-resistant R292K variants in mice. A once-daily administration initiated early after lethal infection hampered body weight loss and completely protected mice from lethality. We observed a time-dependent effect for 24-72-hour delayed DAS181 treatments on morbidity and mortality. The results warrant further investigation of DAS181 for influenza treatment.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
authors.forename: Henju
authors.initials: H
authors.lastname: Marjuki
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
authors.forename: Vasiliy P
authors.initials: VP
authors.lastname: Mishin
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention Battelle Memorial Institute, Atlanta, Georgia.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Chesnokov
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention Battelle Memorial Institute, Atlanta, Georgia.
authors.forename: Juan A
authors.initials: JA
authors.lastname: De La Cruz
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Fry
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
authors.forename: Julie
authors.initials: J
authors.lastname: Villanueva
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Gubareva
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D014779:Virus Replication / Q000502:physiology*; D015047:Zoonoses
chemical_list: D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; C525612:oplunofusp
keywords: Fludase (DAS181); H7N9; R292K; drug resistance; neuraminidase inhibitor; oseltamivir