Aloe-emodin provides dual protection against largemouth bass virus via antiviral activity and host immune enhancement.

Largemouth bass virus (LMBV) is a common pathogen in aquaculture, and with no approved therapies to curb its transmission or mortality, it has caused substantial economic losses to the largemouth bass farming industry. Here, we demonstrate that aloe-emodin (AE), a natural anthraquinone, exhibits potent antiviral activity against LMBV in vitro and in vivo. In vitro, AE (10 mg/L) suppressed viral replication by 91.8 % (p < 0.01), significantly reducing viral titers from 105.92 (96 hpi.) to 104.17 (96 hpi.) TCID50/0.1 mL. AE alleviated the cytopathic effect (CPE) of LMBV infection, maintaining cytoskeletal integrity and nuclear morphology while reducing the overproduction of reactive oxygen species (ROS). In vivo, intraperitoneal injection of AE (0.5 mg/kg) increased the survival rate of LMBV-infected fish from 19 % to 49 % (p < 0.01) and reduced viral titers in the liver, spleen, and kidney. Horizontal transmission experiments demonstrated that AE suppressed viral shedding from donors by 95 % (p < 0.01), while recipient-only and dual donor-recipient treatments reduced transmission efficiency by 57 % and 66 % (p < 0.05), respectively. These results indicated that AE can effectively block the transmission of LMBV among largemouth bass. Additionally, AE increased antiviral interferons (IFN-α/γ) and decreased pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) at the mRNA level. In summary, AE as a host-centered therapeutic that disrupts LMBV pathogenesis through ROS attenuation, immunobalancing, and transmission blockade, offering a translatable strategy for treating aquatic viral diseases.