Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo.

Lei Liu,Tian-Xiu Qiu,Da-Wei Song,Jiong Chen,Guang-Lu Liu,Li-Peng Shan

doi:10.24272/j.issn.2095-8137.2020.037

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 in vitro and in vivo. 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 in vivo 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.

Highlights

Artificial pressures on aquatic ecosystems can lead to the Science PressZoological Research 41(4): 395−409, 2020 395 emergence and outbreak of different diseases in fish
Spring viremia of carp (SVC) is an acute and contagious hemorrhagic disease in cyprinids caused by the spring viremia of carp virus (SVCV), which is a notifiable pathogen on the list of the World Organization for Animal Health (Ahne et al, 2002)
C10 was effective at inhibiting SVCV infection in vitro in a dose-dependent manner (Figure 3A)

Summary

Introduction

Artificial pressures on aquatic ecosystems can lead to the Science PressZoological Research 41(4): 395−409, 2020 395 emergence and outbreak of different diseases in fish. The aquacultural industry is vulnerable to significant economic losses associated with disease, such as viral infections for which there are no efficacious treatments or preventative measures (Balmer et al, 2018; Fujioka et al, 2015). Spring viremia of carp (SVC) is an acute and contagious hemorrhagic disease in cyprinids caused by the spring viremia of carp virus (SVCV), which is a notifiable pathogen on the list of the World Organization for Animal Health (formerly Office International des Epizooties, OIE) (Ahne et al, 2002). With global trade transporting large quantities of live fish between countries, SVCV has spread to Europe (Fijan, 1984), North America (Dikkeboom et al, 2004; Garver et al, 2007), and Asia (Chen et al, 2006; Teng et al, 2007), and poses a serious threat to the carp industry; for example, 4 000 metric tons of carp are lost in Europe each year (Miller et al, 2007). The development of antiviral agents that can be applied for prophylactic or therapeutic treatment against SVCV in aquaculture remains a crucial issue

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Conclusion