Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model.
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.
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: bart.jones@stjude.org.
B G
BG
Jones
R T
RT
Hayden
J L
JL
Hurwitz
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008826:Microbial Sensitivity Tests; D010223:Parainfluenza Virus 2, Human / Q000187:drug effects* / Q000302:isolation & purification; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects* / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D012137:Respiratory System / Q000821:virology; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000821:virology; D019351:Rubulavirus Infections / Q000821:virology; D016205:Sigmodontinae; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; C525612:oplunofusp
Cotton rats; DAS181 virus inhibitor; In vitro; In vivo; Parainfluenza viruses