Evaluation on the antiviral effect of natural product arctigenin against Micropterus salmoides rhabdovirus (MSRV) in vitro and in vivo

Abstract

Micropterus salmoides rhabdovirus (MSRV) is a fish viral pathogen that causes severe disease and huge economic losses in the largemouth bass (M. salmoides) farming industry in aquaculture. Currently, there is no treatment strategy for MSRV. Thus, anti-MSRV drugs are urgently needed. In this study, it was found that the ethanol extract of Arctium lappa L. had good anti-MSRV activity, and the inhibition rate of G and N protein expression of MSRV was >95%. Further studies showed that arctigenin, a natural component of A. lappa L., could inhibit MSRV infection in a dose-dependent mode on grass carp ovary (GCO) cells. In addition, arctigenin could effectively inhibit the cytopathic changes caused by virus and significantly reduce the titer of virus. The pretreatment and post-treatment experiments showed that arctigenin had preventive and therapeutic effects on MSRV infection. TOA and TOR studies indicated that arctigenin may play an antiviral role in the early stage of virus replication. Interestingly, we found that arctigenin treatment significantly inhibited mitochondrial damage in GCO cells by preserving mitochondrial function and maintaining mitochondrial membrane potential levels (ΔΨm). More importantly, arctigenin was also effective against MSRV infection in largemouth bass. The survival rate of infected fish was increased by 16% and 20% respectively by adding 0.5% and 1% arctigenin in the diet. Additionally, the virus titer of the largemouth bass in the arctigenin treatment group was significantly decreased. In summary, arctigenin is confirmed to be a natural product with the excellent anti-MSRV activity, and its application in the treatment of MSRV is promising in aquaculture.