This project has explored a novel class of antiviral drugs to suppress PRRSV replication. These drugs were designed on the basis of PRRSV genomic sequences. Their specific binding to the virus genome is expected to interfere with virus replication. Such compounds were found to be effective in inhibition of PRRSV replication in cell culture, including porcine primary alveolar macrophages, in a dose-responsive manner. Addition of these compounds to cells with experimental PRRSV inoculation reduced the virus yield to less than 0.01% in comparison to the cells of mock treatment control. Combination of two such compounds led to more effective inhibition than individual one. These compounds effectively inhibited virus replication of heterologous strains from North America. Treatment of the primary alveolar macrophages with one such compound protected the cells from PRRSV-induced cell death. In animal test with piglets, administration of one such compound reduced lung lesion and viremia from PRRSV infection. These results indicate that the antiviral compounds are potential anti-PRRSV drugs to complement other strategies to control PRRS. For further questions on this project, please contact me at email@example.com.