A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo

J Infect Dis. 2010 Jul 15;202(2):234-41. doi: 10.1086/653621.


Background: The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid-containing receptors. DAS181, a recombinant sialidase protein containing the catalytic domain of Actinomyces viscosus sialidase, removes cell surface sialic acid, and we proposed that it would inhibit HPIV infection.

Methods: Depletion of sialic acid receptors by DAS181 was evaluated by lectin-binding assays. Anti-HPIV activity in cultured cell lines and in human airway epithelium was assessed by the reduction in viral genomes and/or plaque forming units on treatment. In vivo efficacy of intranasally administered DAS181 was assessed using a cotton rat model.

Results: DAS181-mediated desialylation led to anti-HPIV activity in cell lines and human airway epithelium. Intranasal DAS181 in cotton rats, a model for human disease, significantly curtailed infection.

Conclusions: Enzymatic removal of the sialic acid moiety of HPIV receptors inhibits infection with all tested HPIV strains, both in vitro and in cotton rats. Enzyme-mediated removal of sialic acid receptors represents a novel antiviral strategy for HPIV. The results of this study raise the possibility of a broad spectrum antiviral agent for influenza virus and HPIVs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Animals
  • Cell Line
  • Disease Models, Animal
  • EGF Family of Proteins
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Lymphocyte Depletion
  • Neuraminidase / genetics*
  • Paramyxoviridae Infections / enzymology
  • Paramyxoviridae Infections / immunology*
  • Phosphoproteins / immunology
  • Rats
  • Receptors, Cell Surface / genetics*
  • Recombinant Fusion Proteins / pharmacology*
  • Sigmodontinae
  • Trachea / immunology
  • Trachea / virology
  • Viral Plaque Assay
  • Viral Proteins / immunology


  • AREG protein, human
  • Amphiregulin
  • Areg protein, rat
  • EGF Family of Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • P protein, Human parainfluenza virus 2
  • Phosphoproteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Viral Proteins
  • sialic acid receptor
  • oplunofusp
  • Neuraminidase