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.