Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge

The ef®cacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to pfu of cowpox virus by62±5 3 10 aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals. One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%±100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day 26 to 2 protected 80%±100 % of inl infected mice, whereas 1 inoculation on day 216 to 28 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunode®ciency. Treatment at the time of tail scar-i®cation with vaccinia virus did not block vaccination ef®cacy. Orthopoxviruses pose major risks to human health. By the time smallpox was ®nally eradicated in the late 1970s, the virus had killed tens of millions of people and dis®gured countless millions more [1]. The subsequent discontinuation of vacci