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Antimicrobial Agents and Chemotherapy, July 2003, p. 2223-2230, Vol. 47, No. 7
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.7.2223-2230.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849 ,1 Department of Chemistry, Georgia State University, Atlanta, Georgia 303032
Received 8 October 2002/ Returned for modification 12 December 2002/ Accepted 24 March 2003
Bovine viral diarrhea virus (BVDV) is an economically significant pathogen of cattle and a problematic contaminant in the laboratory. BVDV is often used as an in vitro model for hepatitis C virus during drug discovery efforts. Aromatic dicationic molecules have exhibited inhibitory activity against several RNA viruses. Thus, the purpose of this research was to develop and apply a method for screening the aromatic cationic compounds for in vitro cytotoxicity and activity against a noncytopathic strain of BVDV. The screening method evaluated the concentration of BVDV in medium and cell lysates after 72 h of cell culture in the presence of either a 25 or 5 µM concentration of the test compound. Five of 93 screened compounds were selected for further determination of inhibitory (90 and 50%) and cytotoxic (50 and 10%) concentration endpoints. The screening method identified compounds that exhibited inhibition of BVDV at nanomolar concentrations while exhibiting no cytotoxicity at 25 µM concentrations. The leading compounds require further investigation to determine their mechanism of action, in vivo activity, and specific activity against hepatitis C virus.
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