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

- DAS181 inhibited amplification of six different hPIV clinical isolates in vitro.
- Full inhibition was with drug concentrations ranging between 0.1 and 1 nM.
- DAS181 inhibited amplification of a clinical isolate of hPIV in vivo when drug was administered prior to infection.
- DAS181 inhibited amplification of a clinical hPIV isolate in vivo.
- hPIV inhibition in vivo was most pronounced in the lower respiratory tract.

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 1 nM. An hPIV-3 primary clinical isolate was then tested in a cotton rat model for sensitivity to 0.3-1 mg/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.