Natural ingredient paeoniflorin could be a lead compound against white spot syndrome virus infection in Litopenaeus vannamei

White spot syndrome virus (WSSV) is an important pathogen causing high mortality in the shrimp industry in aquaculture, yet there is no treatment available to date. In order to find a treatment against WSSV infection, this study examined the anti-WSSV activity of eight natural compounds using shrimp larvae as a model. Among the eight compounds, paeoniflorin showed the most obvious anti-WSSV effect, with a maximum protection efficiency of WSSV-infected shrimp >60% at 100 μM. Furthermore, pretreatment and post-treatment experiments revealed that paeoniflorin could prevent and treat WSSV infection in shrimp. The antiviral activity of paeoniflorin in aquaculture water decreased rapidly with time, and the results showed that the stable anti-WSSV activity of paeoniflorin could only remain in water for 1 day. Thus, the dosing pattern of continuous medication changes was evaluated. Obviously, in the model of continuous change of paeoniflorin, WSSV copy numbers in the virus-treated shrimp group still progressively increased, while the virus content in WSSVpaeoniflorin -treated group continued to decrease. Interestingly, paeoniflorin inhibited horizontal transmission of WSSV to a certain extent. Notably, paeoniflorin significantly increased the expression of antimicrobial peptides of shrimp to resist WSSV. In conclusion, paeoniflorin has the potential to protect shrimp against WSSV.