Antiviral effect of pinostrobin, a bioactive constituent of Boesenbergia rotunda, against porcine epidemic diarrhea virus

Abstract

Global swine industry has long been severely affected by the periodic outbreaks of porcine epidemic diarrhea (PED), a deadly infectious disease in piglets caused by the porcine epidemic diarrhea virus (PEDV). Currently, available vaccines and antiviral drugs could not provide effective prevention and treatment of PEDV infection in pigs. In this study, Boesenbergia rotunda (B. rotunda) extract and its major bioactive flavonoid, pinostrobin, were demonstrated to exhibit remarkable anti-PEDV activities with EC50 values of 0.33 ± 0.02 μg/ml and 2.71 ± 0.12 μM, and selectivity indices (SI) of 11.93 and > 184.55, respectively. Results based on a time-of-addition assay showed that pinostrobin blocked PEDV infection mainly at the early stages of infection. More specifically, pinostrobin reduced cell-cell fusion mediated by the viral spike protein, suggesting that the compound may target the virus fusion step. We also synthesized pinostrobin derivatives and explored the impact of pinostrobin structural features to the observed anti-PEDV activity. Results indicated the importance of the hydroxyl group and substituent on the phenyl ring. In summary, this study highlights the potential of B. rotunda extract and its bioactive compound, pinostrobin, as candidates for the development of antiviral drugs to more effectively control PEDV infection.