Rhesus Theta-Defensin Prevents Death in a Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Pulmonary Disease

• DOI: 10.1128/jvi.01363-09
• Publication Date: 2009-08-27T00:50:20Z
• Authors: Christine L. Wohl...; David K. Meyerholz; Stanley Perlman; Haixia Zhou; Dat Tran; Michael E. Selsted; Paul B. McCray
• Keywords: Lung Diseases; Mice, Inbred BALB C; 0303 health sciences; Severe Acute Respiratory Syndrome; Macaca mulatta; Survival Analysis; 3. Good health; Defensins; Disease Models, Animal; Mice; 03 medical and health sciences; Severe acute respiratory syndrome-related coronavirus; Animals; Humans; Lung

ABSTRACT We evaluated the efficacy of rhesus theta-defensin 1 (RTD-1), a novel cyclic antimicrobial peptide, as a prophylactic antiviral in a mouse model of severe acute respiratory syndrome (SARS) coronavirus (CoV) lung disease. BALB/c mice exposed to a mouse-adapted strain of SARS-CoV demonstrated 100% survival and modest reductions in lung pathology without reductions in virus titer when treated with two intranasal doses of RTD-1, while mortality in untreated mice was ∼75%. RTD-1-treated, SARS-CoV-infected mice displayed altered lung tissue cytokine responses 2 and 4 days postinfection compared to those of untreated animals, suggesting that one possible mechanism of action for RTD-1 is immunomodulatory.