Antiviral effect of 7-(4-benzimidazole-butoxy)-coumarin on rhabdoviral clearance via Nrf2 activation regulated by PKCα/β phosphorylation

Liu, Lei; Shen, Yufeng; Hu, Yang; Lu, Jian-Fei

doi:10.1016/j.fsi.2018.09.054

Cited by 32 publications

(18 citation statements)

References 47 publications

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“…Although C10 did not reduce SVCV replication in the early stage of viral infection, it significantly reduced SVCV replication during viral biosynthesis, as observed in time-of-addition and time-of-removal analyses. Compared with other 7-hydroxy-imidazole coumarin medicines, such as 7-(3-benzimidazole propoxy) coumarin (B4) ( Qiu et al, 2020 ), 7-(4-(4-methyl-imidazole))-coumarin (C2) ( Liu et al, 2019a ), 7-(4-benzimidazole-butoxy)-coumarin (BBC) ( Liu et al, 2018 ; Shen et al, 2018 ), 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-5H-chromeno[4,3-d] pyrimidin-5-one (S5) ( Song et al, 2020 ) and 7-(6-(2-methyl-imidazole))-coumarin (D5) ( Liu et al, 2019b ), C10 demonstrated lower acute toxicity in zebrafish, and could therefore be used as a viable agent for preventing and controlling SVCV infection.…”

Section: Discussionmentioning

confidence: 99%

“…In general, a virus triggers imbalance of intracellular redox cycling, resulting in ROS generation exceeding endogenous antioxidant defense in host cells. In contrast, the intracellular redox state can affect viral replication in host cells ( Garaci et al, 1997 ; Michalek et al, 2008 ; Liu et al, 2018 ). It has been reported that prolonged stimulation with SVCV can disrupt the balance of intracellular redox cycling in fish ( Yuan et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, exponential enhancement of viral loads tends to break through defense easily and exceed the threshold in a time-dependent manner, resulting in serious damage in fish ( Workenhe et al, 2010 ). Hydroxyl coumarins are regarded as antioxidant drugs in the formation and scavenging of ROS to induce the Nrf2-ARE signaling pathway against SVCV ( Liu et al, 2017 , 2018 ; Peng et al, 2013 ). In this sense, C10 treatment not only protected mitochondria, but also stimulated antioxidant capacity in zebrafish by maintaining antioxidant resistance, thereby simultaneously contributing to SVCV replication inhibition.…”

Section: Discussionmentioning

confidence: 99%

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

Liu¹,

Song²,

Liu³

et al. 2020

Zoological Research

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Liu¹,

Song²,

Liu³

et al. 2020

Zoological Research

Self Cite

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“…The results above indicated that SVCV replication could be significantly inhibited by Ani treatment in vitro. (Liu et al, 2018;Shen et al, 2018a, b;Shen et al, 2019). The results in Fig.…”

Section: Antiviral Activity Of Ani Against Svcv Infection In Epc Cellsmentioning

confidence: 99%

“…In addition, some researches have been conducted to develop anti-SVCV drugs. Previous studies reported that several natural products and their derivatives showed a good anti-SVCV potential Liu et al, 2017Liu et al, , 2018Liu et al, 2019;Shen et al, 2018a, b;Shen et al, 2019). These findings indicate that it is feasible to control SVCV infection by drug treatment.…”

Section: Introductionmentioning

confidence: 98%

Antiviral activity of anisomycin against spring viraemia of carp virus in epithelioma papulosum cyprini cells and zebrafish

Shen

Zhu

et al. 2019

Virus Research

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A B S T R A C T Spring viraemia of carp (SVC) caused by spring viraemia of carp virus (SVCV) is an acute and highly lethal viral disease of cyprinid fish. However, effective therapy for SVC is still scarce until now. Here we evaluated the inhibition of anisomycin (Ani), a metabolite produced by Streptomyces griseolus, on the replication of SVCV in vitro and in vivo. Our results demonstrated that Ani could suppress SVCV replication with the maximum inhibitory rate > 95% in epithelioma papulosum cyprini (EPC) cells. And the half maximal inhibitory concentrations (IC 50 ) of Ani on SVCV glycoprotein (G), nucleoprotein (N) and phosphoprotein mRNA expressions were 21.79, 13.13 and 12.24 nM, respectively. Besides, Ani decreased SVCV-induced cytopathic effects and nucleus damages. As expected, Ani also showed a strong anti-SVCV activity in vivo, as indicated by inhibiting viral gene expression and increasing the survival rate of zebrafish. Intraperitoneal injection of Ani increased the survival rate of zebrafish by 30% and markedly inhibited the expressions of G and N mRNA by > 60% in kidney and spleen at day 1 and day 4 post-infection. Results so far suggest that Ani as a powerful agent against SVCV can be applied to the control of SVC in aquaculture.

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Viral infections in cultured fish and shrimps: current status and treatment methods

et al. 2021

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Antiviral effect of 7-(4-benzimidazole-butoxy)-coumarin on rhabdoviral clearance via Nrf2 activation regulated by PKCα/β phosphorylation

Cited by 32 publications

References 47 publications

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

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

Antiviral activity of anisomycin against spring viraemia of carp virus in epithelioma papulosum cyprini cells and zebrafish

Viral infections in cultured fish and shrimps: current status and treatment methods

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