DRACO inhibits porcine reproductive and respiratory syndrome virus replication in vitro

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Current vaccination strategies and antiviral drugs against PRRSV are still inadequate. Therefore, there is an urgent need for new antiviral strategies to control PRRSV. Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) is a synthetic construct consisting of a dsRNA detection domain, an apoptosis induction domain, and a transduction tag. It has been shown to have broad-spectrum antiviral activity, but there have been no reports regarding its effect on PRRSV. Here, we demonstrate that DRACO exhibits robust antiviral activity against PRRSV infection by suppressing virus RNA and protein synthesis in both Marc-145 cells and porcine alveolar macrophages (PAMs). In addition, DRACO still exhibited strong anti-PRRSV activity when viral replication was enhanced by knockdown of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in Marc-145 cells. Furthermore, in PAMs, DRACO was capable of inducing IL-6 expression and reducing Hsp70 expression, which might contribute to the inhibition of PRRSV infection. Collectively, our results imply that DRACO holds promise as a novel anti-PRRSV therapeutic drug.