Efficacy of RD3-0028 aerosol treatment against respiratory syncytial virus infection in immunosuppressed mice.
RD3-0028, a benzodithiin compound, has antiviral activity against respiratory syncytial virus (RSV) in cell culture. We used a mouse model of RSV infection to determine the in vivo effect of RD3-0028. Cyclophosphamide (CYP)-treated, immunosuppressed mice were inoculated intranasally. The lungs of the mice were removed on day 4. The virus titers of the lungs of RD3-0028-treated mice were compared to the virus titers of the lungs of virus-inoculated, untreated control mice. In an effort to increase the therapeutic effectiveness of this compound, RD3-0028 was administered by aerosol to RSV-infected mice by using a head-exposure system. Aerosols generated from reservoirs containing RD3-0028 (7 mg/ml) administered for 2 h twice daily for 3 days significantly reduced the pulmonary titer of RSV-infected mice. It is clear that the minimal effective dose of RD3-0028 for RSV-infected mice is significantly less than that of ribavirin, the only compound currently available for use against RSV disease. Furthermore, the RD3-0028 aerosol administration appeared to protect the lungs of infected, CYP-treated mice against tissue damage, as evidenced by the preservation of the lung architecture and a reduction in pulmonary inflammatory infiltrates. RD3-0028 aerosol was not toxic for mice at the therapeutic dose. The present study demonstrates the effectiveness of aerosol administration of RD3-0028 for RSV-infected mice.
Sudo
K
K
Rational Drug Design Laboratory, Fukushima, Japan.
Watanabe
W
W
Konno
K
K
Sato
R
R
Kajiyashiki
T
T
Shigeta
S
S
Yokota
T
T
D000336:Aerosols / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D017063:Outcome Assessment, Health Care; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects
D000336:Aerosols; D000998:Antiviral Agents; D006571:Heterocyclic Compounds; C119093:RD3 0028