Recombinant superoxide dismutase (SOD) administered by aerosol inhibits respiratory syncytial virus infection in cotton rats.
Recombinant (r) human (hu) manganese (Mn) and copper-zinc (CuZn) superoxide dismutase (SOD) were evaluated for their cytotoxicity and antiviral activity against respiratory syncytial virus (RSV) in tissue culture and in cotton rats. No apparent cytotoxicity or inhibition of RSV was observed in the tissue culture studies (both compounds had IC50 and EC50 values > or = 1000 micrograms/ml and a selective index = 1). However, significant reductions in mean pulmonary RSV titers (ranging between 0.5 and 1.9 log10/g of lung compared with the mean pulmonary viral titers detected in similarly inoculated, placebo-treated control animals) were seen in most of the experiments, in which experimentally infected cotton rats were exposed to continuous small-particle aerosols (reservoir concentrations > or = 20 mg/ml) containing either rhuMnSOD or rhuCuZnSOD. This protective effect was dose dependent and not observed when either rSOD compound was administered parenterally (intraperitoneally) or intranasally. No toxic effects were noted in any of the cotton rats exposed to aerosols of either rhuMn or CuZnSOD; nor was any evidence of drug-induced histopathology observed in sections of lung prepared from these animals.
Wyde
P R
PR
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Moore
D K
DK
Pimentel
D M
DM
Gilbert
B E
BE
Nimrod
R
R
Panet
A
A
D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D003300:Copper; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008168:Lung / Q000378:metabolism; D008345:Manganese; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D016205:Sigmodontinae; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D015032:Zinc
D000336:Aerosols; D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D008345:Manganese; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc