Synthesis and antiviral activity of a new coumarin derivative against spring viraemia of carp virus.

Abstract

Coumarin as a lead structure have received a considerable attention in the last three decades for the discovery of antiviral agents. Our previous study indicated that imidazole coumarins possessed antiviral activities against SVCV. Based on the structure-activity relationship in that study, a new imidazole coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), was designed, synthesized and its anti-SVCV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC), we found that BBC (IC = 0.56 mg/L) possessed a higher antiviral activity than those imidazole coumarins in our previous study. Besides, BBC can significantly inhibit cell death and reduce cellular morphological damage induced by SVCV. Our further data indicated that intraperitoneal injection of BBC increased the survival rate of zebrafish by 17.5%, decreased viral titer in fish body and inhibited SVCV glycoprotein expression in kidney and spleen. In uninfected zebrafish, the expression levels of ifnγ, ifnφ1, ifnφ2 and rig1 genes were up-regulated after BBC treatment, which indicated that BBC could activate interferon response. In addition, data of the antioxidant enzymes activities and results of the antioxidant enzymes-related genes expressions suggested BBC could reduce SVCV-induced oxidative damage in infected zebrafish. Altogether, BBC is expected to be a therapeutic agent against SVCV infection in the field of aquaculture.