Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection <i>in vitro</i> and <i>in vivo</i>
Lei Liu, 宁波大学农产品质量安全危害因子与风险防控国家重点实验室，浙江 宁波315211，中国, Dawei Song, Guanglu Liu, Li‐Peng Shan, Tian-Xiu Qiu, Jiong Chen, 宁波大学梅山校区海洋学院生物化学与分子生物学实验室，浙江 宁波 315832，中国, 宁波大学梅山校区教育部应用海洋生物技术重点实验室，浙江 宁波 315832，中国, 周口师范学院化学与化工学院，河南 周口 466001，中国
Abstract
Spring viremia of carp virus (SVCV) causes devastating losses in aquaculture. Coumarin has an advantageous structure for the design of novel antiviral agents with high affinity and specificity. In this study, we evaluated a hydroxycoumarin medicine, i.e., 7-(6-benzimidazole) coumarin (C10), regarding its anti-SVCV effects <i>in vitro</i> and <i>in vivo</i>. Results showed that up to 12.5 mg/L C10 significantly inhibited SVCV replication in the epithelioma papulosum cyprini (EPC) cell line, with a maximum inhibitory rate of >97%. Furthermore, C10 significantly reduced cell death and relieved cellular morphological damage in SVCV-infected cells. Decreased mitochondrial membrane potential (ΔΨm) also suggested that C10 not only protected mitochondria, but also reduced apoptosis in SVCV-infected cells. For <i>in vivo</i> studies, intraperitoneal injection of C10 resulted in an anti-SVCV effect and substantially enhanced the survival rate of virus-infected zebrafish. Furthermore, C10 significantly enhanced antioxidant enzyme activities and decreased reactive oxygen species (ROS) to maintain antioxidant-oxidant balance within the host, thereby contributing to inhibition of SVCV replication. The up-regulation of six interferon (IFN)-related genes also demonstrated that C10 indirectly activated IFNs for the clearance of SVCV in zebrafish. This was beneficial for the continuous maintenance of antiviral effects because of the low viral loads in fish. Thus, C10 is suggested as a therapeutic agent with great potential against SVCV infection in aquaculture.