Treatment with RTD-1 protects mice against lethality of SARS-CoV infection. (A and B) BALB/c mice 6 to 8 weeks old were treated with sham control (40 μl phosphate-buffered saline, no virus), RTD-1 alone (125 μg [∼5 mg/kg] intranasal RTD-1 15 min prior to infection, followed by an identical dose 18 h later), SARS-CoV alone (3 × 105 PFU MA15 intranasally in 40 μl phosphate-buffered saline), or RTD-1 followed with SARS-CoV infection. Mice were monitored daily for weight loss (A) and survival (B) (n = 6 or 7/group). SARS-CoV-infected mice without RTD-1 treatment had a 30% survival rate and 25% decrease in weight in those that survived (*, P ≤ 0.05 by Student's t test for SARS alone versus all other groups). Data presented in panels A and B are representative of two independent experiments. (C) Lung tissue was harvested from mice, and viral titer levels were determined. (D) RTD-1 has no direct antiviral effect on SARS-CoV. Viral titers were determined using Vero cells and samples of 1 × 105 PFU SARS-CoV (Urbani) that were preincubated for 30 min at 37°C with RTD-1 in serum-free phosphate-buffered saline at the indicated concentrations prior to plaque assay in Vero cells. Results in panels A, C, and D are presented as means ± standard errors (A and B, n = 6 or 7; C and D, n = 3). All experiments were performed under biosafety level 3 containment. This study was approved by the University of Iowa Animal Care and Use Committee.