Antiviral activity of micafungin against enterovirus 71

Kim, Chonsaeng; Kang, Hyunju; Kim, Dongeun; Song, Jae-Hyoung; Choi, Min; Kang, Minho; Lee, Kyungjin; Kim, Hae Soo; Shin, Jin Soo; Jeong, Hyejeong; Jung, Sunhee; Han, Sang‐Bae; Kim, Jong Heon; Ko, Hyun‐Jeong; Lee, Chong-Kyo; Kim, Meehyein; Cho, Sungchan

doi:10.1186/s12985-016-0557-8

Cited by 33 publications

(34 citation statements)

References 39 publications

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“…at 89.2%, demonstrating that ITZ strongly suppresses viral RNA replication or polyprotein processing [ 87 ]. Another study evaluated a total of 968 FDA-approved drugs as potential antivirals using both EV-71 and CV-B3 replicon systems [ 96 ]. Vero cells were transfected with EV-71 replicon RNA and simultaneously treated with the compounds at 10 µM concentration.…”

Section: Non-enveloped Virusesmentioning

confidence: 99%

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Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Fernandes

Freire

Bueno

et al. 2020

Viruses

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Single-stranded positive RNA ((+) ssRNA) viruses include several important human pathogens. Some members are responsible for large outbreaks, such as Zika virus, West Nile virus, SARS-CoV, and SARS-CoV-2, while others are endemic, causing an enormous global health burden. Since vaccines or specific treatments are not available for most viral infections, the discovery of direct-acting antivirals (DAA) is an urgent need. Still, the low-throughput nature of and biosafety concerns related to traditional antiviral assays hinders the discovery of new inhibitors. With the advances of reverse genetics, reporter replicon systems have become an alternative tool for the screening of DAAs. Herein, we review decades of the use of (+) ssRNA viruses replicon systems for the discovery of antiviral agents. We summarize different strategies used to develop those systems, as well as highlight some of the most promising inhibitors identified by the method. Despite the genetic alterations introduced, reporter replicons have been shown to be reliable systems for screening and identification of viral replication inhibitors and, therefore, an important tool for the discovery of new DAAs.

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Section: Non-enveloped Virusesmentioning

confidence: 99%

“…Similar results were obtained for Vero cells transfected with CV-B3 replicon RNA. Nevertheless, the precise mechanism of the antiviral effect of Micafungin on EV-71 was not determined [ 96 ].…”

Section: Non-enveloped Virusesmentioning

confidence: 99%

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Fernandes

Freire

Bueno

et al. 2020

Viruses

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“…MTT assay was used for measuring cell viability as described previously [40]. Cell viability was calculated as a percentage relative to the control.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…Plasmids p53CB3-LUC and pRibFluc-EV71, which contain the firefly luciferase gene in place of the P1 capsid coding region of CVB3 and EV71 viral genomes, were kindly provided by Frank J. M. van Kuppeveld (Utrecht University, The Netherlands) [23,24]. Synthesis of CVB3 and EV71 replicon RNAs and replicon assays were performed as previously described [40]. Briefly, HeLa cells (3×10 5 cells/well) on a 6-well plate were transfected with 0.4 μg of replicon RNA, split into 96well plates (2×10 4 cells/well), and simultaneously treated with nucleosides, nucleobases or pyrimidine biosynthetic intermediates in the presence of gemcitabine.…”

Section: Replicon Assaymentioning

confidence: 99%

Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion

et al. 2017

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Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.

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“…Enterovirus 71 (EV71) and Coxsackie virus A16 are common etiological agents of HFMD, among which, EV71 can cause severe central nervous system damage and multiple-organ dysfunction and even become life threatening (2). EV71 infection can cause immune system dysfunction; T lymphocyte subsets can secrete a variety of inflammatory cytokines, which can worsen the disease symptoms (3).…”

Section: Introductionmentioning

confidence: 99%

The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway

Zhu

Gao

et al. 2017

Experimental and Therapeutic Medicine

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Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study. Peripheral vein blood samples were collected from each individual, and used to isolate peripheral blood mononuclear cells (PBMCs) for mRNA extraction and sera for measuring levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6 and IL-10. The average expression levels of TLR3, TLR4, TLR7 and TLR8 mRNA in PBMCs of children with severe HFMD were significantly higher than those in the other children, the lowest values were found in the healthy control group (P<0.05). The expression levels of TLR2 and TLR9 mRNA were not significantly different (P>0.05) among the groups. Additionally, the expression levels of TNF-α, IFN-γ, IL-6 and IL-10 in the serum of the children in the severe group were significantly higher than those in the other two groups, and the lowest values were again found in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with the TNF-α, IFN-γ, IL-6 and IL-10 levels in the serum (P<0.05). Furthermore, the expression levels of the ERK, JNK and p38 mRNA in PBMCs of children in the severe group were significantly higher than those in the other two groups, with the lowest values being in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with ERK, JNK and p38 mRNA levels (P<0.05). The results of our study seem to indicate that the high expression levels of TLR3, TLR4, TLR7 and TLR8 induced in severe EV71 HFMD regulate the expression of cytokines by MAPK signaling pathway and negatively affect the ability of the organism to resolve the infection. Further studies are needed to test the hypothesis that immuno-modulation would be an effective treatment approach in pediatric cases of severe HFMD.

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Antiviral activity of micafungin against enterovirus 71

Cited by 33 publications

References 39 publications

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion

The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway

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