Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection <i>in vitro</i> and <i>in vivo</i>

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.

Comparative proteomic analysis provides insight into the key proteins as potential targets underlying the effect of malachite green against Ichthyophthirius multifiliis

“…In this study, the iTRAQ‐based quantitative proteomic analysis was used to determine the proteomic changes among I. multifiliis collected from the infected fish exposed to MG at 0.5 mg/L for 0, 0.5 and 3 hr, respectively. The genes of differentially expressed proteins were further verified in the transcription level by RT‐qPCR analysis (Liu et al., 2020) and morphological observation by transmission electron microscopy (TEM) and fluorescent microscope. Given the toxicity of MG and the fact that it cannot be used with food fish, our results identified proteins and pathways associated with MG treatment that could help in the identification and testing of other potentially useful drugs that target similar proteins or pathways without the negative side effects of MG, which could be tested as possible treatments for I. multifiliis .…”

Small Molecule Inhibitors of White Spot Syndrome Virus: Promise in Shrimp Seedling Culture

“…Moreover, the component complexity and cost-effectivity of these strategies remain limitations of these approaches [ 28 ]. Thus, naturally occurring biological compounds have been isolated and purified from plants or synthesized as potential antiviral agents [ 19 , 21 , 24 , 31 , 32 , 33 ]. For example, epigallocatechin gallate is a promising therapeutic agent against grass carp reovirus (GCRV) infection by blocking its binding to laminin receptors [ 34 ]; saikosaponin D efficiently suppressed spring viremia of carp virus (SVCV) replication in vivo, prolonging the survival of zebrafish and common carp [ 35 ].…”

“…One class of natural compounds that has been extensively studied is coumarins, which are phytochemicals occurring naturally in plants, bacteria, and fungi. Coumarins target various cellular pathways, inhibiting the growth and replication of viruses [ 16 , 17 , 18 , 19 , 20 ]. In addition, a coumarin (benzo-α-pyrone) with an oxygen heterocycle and the parent chemical structure is considered to be the leading compound for further chemical synthesis or structural modifications [ 16 ].…”

“…Earlier synthetic coumarins with a variety of pharmacophoric groups at the C-3, C-4, and C-7 positions have been screened intensively for antiviral effects, based on the correlation between structural characteristics and biological activities [ 21 ]. In addition to its application in human viral diseases, it has the advantages of being stable, soluble, and of low molecular weight, without any adverse side effects and toxicity, making coumarin derivatives candidate drugs for use against aquatic viruses [ 18 , 19 , 22 , 23 , 24 ], including WSSV.…”

Potential aquatic environmental risks of trifloxystrobin: Enhancement of virus susceptibility in zebrafish through initiation of autophagy

“…TFS can induce embryonic lesions, decrease hatching success, and increase oxidative stress in zebrafish embryos by increasing reactive oxygen species (ROS) and malonaldehyde (MDA) content, and inhibiting superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and antioxidant system-related mRNA genes (i.e., Mn-SOD , Cu/Zn-SOD , CAT , Nrf2 , and Bcl2 ) ( Li et al, 2018 ; Zhu et al, 2015a ). These cellular components are crucial for maintaining antiviral resistance in fish against the acutely contagious and hemorrhagic SVC disease ( Liu et al, 2020a ; Yuan et al, 2014 ). Therefore, the above studies raise concern that chronic exposure to TFS at environmental concentrations may affect the resistance of aquatic organisms to pathogens.…”