DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection.
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.
Belser
Jessica A
JA
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Lu
Xiuhua
X
Szretter
Kristy J
KJ
Jin
Xiaoping
X
Aschenbrenner
Laura M
LM
Lee
Alice
A
Hawley
Stephen
S
Kim
Do Hyong
DH
Malakhov
Michael P
MP
Yu
Mang
M
Fang
Fang
F
Katz
Jacqueline M
JM
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
D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; D014760:Viral Fusion Proteins; C525612:oplunofusp