William A. Cafruny¹, Richard G. Duman¹, Raymond R. Rowland², Eric A. Nelson³, and Grace H. Wong⁴

¹Sanford School of Medicine, University of South Dakota, 414 E. Clark St., Vermillion, S.D. 57069. ²Department of Diagnostic Medicine and Pathobiology, L-229 Mosier Hall, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506. ³Department of Veterinary Science/ADRDL, North Campus Drive, South Dakota State University, Brookings, SD 57007. ⁴Actokine Therapeutics, 12 Middlesex Rd. #411, Chestnut Hill, MA 02467.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolonecontaining compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs). Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ) to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV) was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.