Tilmicosin was investigated in a stable porcine alveolar macrophage cell line for its antiviral activity against types 1 and 2 porcine reproductive and respiratory syndrome virus (PRRSV). Tilmicosin exhibited strong antiviral effects on both genotypes of PRRSV replication in cultured porcine alveolar macrophages. The antiviral activity was more potent for type 1 PRRSV as indicated by reduction in infectious virus yield of nearly 43-fold for type 1 as compared to 14-fold for type 2. Real-time RT-PCR for detection of viral nucleocapsid gene confirmed the reduction of infectious virus titer in the presence of tilmicosin.
Lysosomotropic and ion-channel blocking agents efficiently inhibited PRRSV replication, suggesting that the antiviral mechanism of tilmicosin is likely associated with the alteration of endosomal pH and possibly the ion-channel activity on the viral membrane. This study indicates that tilmicosin may have potential as an early treatment or preventative measure against PRRSV infections, especially for areas where the type 1 genotype is prevalent.
In the present research, the antiviral effects of tilmicosin were investigated on the two genotypes of PRRSV. The data demonstrated the inhibitory effects of tilmicosin on PRRSV in PAM cells and supported the initial hypothesis that the possible mechanism of action for tilmicosin is associated with the alteration of endosomal pH and the disassembly of virions. Specifically, increased pH in the endosome would result in inefficient disassembly of the viral capsid and insufficient uncoating of the virus. Interestingly, although the inhibitory activity was observed for both genotypes, the compound was more potent for type 1 than for type 2 PRRSV.
Overall, our study provides experimental confirmation as well as a possible mechanism of action for tilmicosin efficacy that has been empirically observed in the clinical setting. Since vaccination approaches have shown limited success, the therapeutic potential of tilmicosin as an early treatment or preventive measure for PRRSV infection should be investigated further.