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: Jessica A Belser, Xiuhua Lu, Kristy J Szretter, Xiaoping Jin, Laura M Aschenbrenner, Alice Lee, Stephen Hawley, Do Hyong Kim, Michael P Malakhov, Mang Yu, Fang Fang, Jacqueline M Katz
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 196 Issue 10 Pg. 1493-9 (Nov 15 2007) ISSN: 0022-1899 [Print] United States
• PMID: 18008229 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Recombinant Fusion Proteins
• Sialic Acids
• Viral Fusion Proteins
• oplunofusp

Topics

• Animals
• Antiviral Agents (administration & dosage, pharmacology)
• Brain (virology)
• Disease Models, Animal
• Female
• Humans
• Influenza A Virus, H5N1 Subtype (drug effects, pathogenicity)
• Influenza, Human (prevention & control, virology)
• Lung (virology)
• Mice
• Mice, Inbred BALB C
• Recombinant Fusion Proteins (pharmacology)
• Sialic Acids (administration & dosage, pharmacology)
• Viral Fusion Proteins (administration & dosage, pharmacology)