| 苯基吡啶酮衍生物影响猪δ冠状病毒复制的作用分析 |
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| 引用本文： | 姚晨,郭萌,胡慧,史晨曦,杨国宇.苯基吡啶酮衍生物影响猪δ冠状病毒复制的作用分析[J].畜牧兽医学报,2022,53(9):3190-3198. |
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| 作者姓名： | 姚晨 郭萌 胡慧 史晨曦 杨国宇 |
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| 作者单位： | 1. 河南农业大学动物医学院, 郑州 450002;2. 河南农业大学农业农村部动物生化与营养重点实验室, 郑州 450002;3. 河南省动物性食品安全重点实验室, 郑州 450002 |
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| 基金项目： | 河南省杰出青年基金项目（202300410192） |
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| 摘 要： | 本研究旨在探讨苯基吡啶酮衍生物JIB-04对猪δ冠状病毒（porcine deltacoronavirus，PDCoV）的抗病毒作用，并初步研究可能的作用机制。首先应用CCK-8方法检测不同浓度JIB-04作用后的细胞活力，并计算半数毒性浓度（CC50）和半数有效浓度（EC50）。应用TCID50方法检测JIB-04预处理和共处理对PDCoV复制的影响，检测JIB-04处理对PDCoV吸附或入侵细胞的影响。最后，应用qRT-PCR、TCID50和Western blot方法检测JIB-04处理对不同时间点病毒复制的影响。结果表明，JIB-04在所有受试浓度下均不影响LLC-PK细胞的活力，CC50>640 μmol·L-1，EC50=0.216 μmol·L-1，SI指数>2 963。与未处理的病毒感染组相比，JIB-04处理极显著降低了PDCoV的滴度（P<0.001），但对PDCoV吸附和入侵过程没有影响。感染6 h后，与未处理的病毒感染组相比，JIB-04处理组PDCoV滴度极显著下降（P<0.01）；感染12和24 h后，PDCoV滴度、基因组拷贝数、N蛋白表达水平均极显著下降（P<0.01）。JIB-04的细胞毒性较低，药物选择性指数较高，在体外能抵抗PDCoV感染，可以作为潜在的抗病毒药物。在PDCoV感染过程中，JIB-04能够抑制病毒核酸和蛋白质的合成，抑制病毒的复制。
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| 关 键 词： | 苯基吡啶酮衍生物JIB-04 抗病毒 猪δ冠状病毒 |
| 收稿时间： | 2022-01-28 |
Effects of Phenylpyridinone Derivative on the Replication of Porcine Deltacoronavirus |
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| YAO Chen,GUO Meng,HU Hui,SHI Chenxi,YANG Guoyu.Effects of Phenylpyridinone Derivative on the Replication of Porcine Deltacoronavirus[J].Acta Veterinaria et Zootechnica Sinica,2022,53(9):3190-3198. |
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| Authors: | YAO Chen GUO Meng HU Hui SHI Chenxi YANG Guoyu |
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| Institution: | 1. College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, China;2. Key Laboratory of Animal Biochemistry and Nutrition of Ministry of Agriculture and Rural Affairs, Henan Agricultural University, Zhengzhou 450002, China;3. Henan Province Key Laboratory of Animal Food Safety, Zhengzhou 450002, China |
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| Abstract: | The purpose of this study was to investigate the antiviral effect of phenylpyridinone derivative JIB-04 on porcine deltacoronavirus (PDCoV), and explore the possible mechanism. Cell viability after treatment with different concentrations of JIB-04 was detected by CCK-8, and the 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) were calculated. TCID50 method was used to detect the effects of JIB-04 pretreatment and co-treatment on PDCoV replicationand the effect of JIB-04 treatment on virus attachment and penetration. Finally, qRT-PCR, TCID50 and Western blot methods were used to detect the effect of JIB-04 on virus replication at different times post infection. The results showed that JIB-04 did not affect the cell viability of LLC-PK cells at all tested concentrations, and CC50>640 μmol·L-1, EC50=0.216 μmol·L-1, and SI index is greater than 2 963. Compared with untreated virus infection group, JIB-04 treatment significantly reduced the virus titer (P<0.001), but it had no effect on attachment or penetration of PDCoV. At 6 h post infection, compared with untreated virus infection group, virus titer in JIB-04 treatment group was significantly decreased (P<0.01). At 12 and 24 h post infection, virus titer, genome copy number, and N protein expression level all significantly decreased (P<0.01). JIB-04 has a low cytotoxicity and a high selective index, and can protect against PDCoV infection in vitro, making it a potential antiviral drug. JIB-04 can inhibit synthesis of viral RNA, protein and PDCoV replication. |
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| Keywords: | phenylpyridinone derivative JIB-04 antiviral porcine deltacoronavirus |
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