Baicalein inhibits Micropterus salmoides rhabdovirus replication in vitro and in vivo

Micropterus salmoides rhabdovirus (MSRV) is one of the leading threats to largemouth bass farming and there is an urgent need for anti-MSRV drug development. Baicalein, a trihydroxyflavone, isolated from Scutellaria baicaleinsis (Huangqin), possesses numerous pharmacological properties, including widespread antiviral activities. This study aimed to determine the role of baicalein in MSRV replication and to investigate its underlying mechanisms. Cell viability and drug treatment assays showed that baicalein significantly inhibited MSRV replication at the concentration range of 4–40 μM without obvious cytotoxicity. Pretreatment assay indicated that treating EPC cells with baicalein before MSRV infection has no significant inhibition on MSRV replication, suggesting the antiviral action of baicalein might not target to MSRV receptor or induce host cells to produce antiviral factors. Time of addition assays suggested that baicalein is effective throughout the entire MSRV life cycle, particularly in the early stage. Further studies showed that baicalein inhibited both the attachment of MSRV and its release processes. The direct virucidal assay revealed baicalein directly attenuated MSRV infectivity, which may partly account for its anti-MSRV effect. In vivo experiments showed that baicalein significantly improved the survival rate of MSRV-challenged fish by 35.0 %. Altogether, baicalein exhibited a strong anti-MSRV activity and might be a promising therapeutic drug against MSRV infection.