Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease.
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 approximately 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.
Wohlford-Lenane
Christine L
CL
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Meyerholz
David K
DK
Perlman
Stanley
S
Zhou
Haixia
H
Tran
Dat
D
Selsted
Michael E
ME
McCray
Paul B
PB
D000818:Animals; D023082:Defensins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008171:Lung Diseases / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D008253:Macaca mulatta / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D016019:Survival Analysis
D023082:Defensins; C450142:theta-defensin