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Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model.

Abstract
DAS181 is a novel drug in development for the treatment of influenza as well as human parainfluenza viruses (hPIVs). Previous studies demonstrated that DAS181 inhibited laboratory strains of hPIV, but no tests were conducted with primary clinical isolates of hPIV. To fill this gap, we studied six primary isolates including hPIV-2 and hPIV-3. First tests showed that the amplification of all viruses in vitro was reproducibly inhibited with DAS181 drug concentrations ranging between 0.1 and 1nM. An hPIV-3 primary clinical isolate was then tested in a cotton rat model for sensitivity to 0.3-1mg/kg drug treatments. Results showed that virus amplification in the lower respiratory tract was significantly and reproducibly inhibited by drug. Together, experiments demonstrated that DAS181 inhibited primary clinical isolates of hPIV in vitro and in vivo at doses similar to those previously described for inhibition of laboratory hPIV and influenza virus isolates.
AuthorsB G Jones, R T Hayden, J L Hurwitz
JournalAntiviral research (Antiviral Res) Vol. 100 Issue 2 Pg. 562-6 (Nov 2013) ISSN: 1872-9096 [Electronic] Netherlands
PMID24076357 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Antiviral Agents
  • Recombinant Fusion Proteins
  • oplunofusp
Topics
  • Animals
  • Antiviral Agents (pharmacology, therapeutic use)
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Microbial Sensitivity Tests
  • Parainfluenza Virus 2, Human (drug effects, isolation & purification)
  • Parainfluenza Virus 3, Human (drug effects, isolation & purification)
  • Recombinant Fusion Proteins (pharmacology, therapeutic use)
  • Respiratory System (virology)
  • Respirovirus Infections (drug therapy, virology)
  • Rubulavirus Infections (virology)
  • Sigmodontinae
  • Treatment Outcome
  • Viral Load

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