Neferine inhibits PRRSV infection by disrupting p65 nuclear translocation

Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), imposes substantial economic losses on the global swine industry due to its profound impact on pig health and production efficiency. The main clinical manifestations are reproductive disorders such as miscarriage, stillbirth or weak foetuses in sows, as well as severe respiratory diseases in pigs of all ages. Currently, due to the high genomic diversity, antigen heterogeneity, and antibody-dependent enhancement effects of PRRSV, vaccination strategies cannot effectively control PRRSV infection. It is also difficult to control these viral infectious diseases with antiviral drugs. In this study, we demonstrate that neferine (Nef), a natural compound derived from lotus seeds, inhibits NF-κB activation during PRRSV infection. Consequently, Nef effectively suppresses PRRSV gene expression and virion replication in the PRRSV-infected Marc-145 cell line. Further studies demonstrated that Nef attenuates the nuclear translocation of p65 triggered by PRRSV infection, consequently mitigating the excessive production of inflammatory cytokines in infected cells. This anti-inflammatory mechanism may contribute to its observed antiviral efficacy against PRRSV. As a result, we conclude that Nef may be an effective clinical treatment for the acute occurrence and transmission of PRRSV infections. Furthermore, PRRSV is thought to be responsible for an increase in proinflammatory cytokines.