苯基吡啶酮衍生物影响猪δ冠状病毒复制的作用分析

doi:10.11843/j.issn.0366-6964.2022.09.033

Abstract

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.

Key words: phenylpyridinone derivative JIB-04, antiviral, porcine deltacoronavirus

CLC Number:

R978.7

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.

References 27

[1]	LU R J, ZHAO X, LI J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:implications for virus origins and receptor binding[J]. Lancet, 2020, 395(10224):565-574.
[2]	LI F. Structure, function, and evolution of coronavirus spike proteins[J]. Annu Rev Virol, 2016, 3:237-261.
[3]	WANG Q H, VLASOVA A N, KENNEY S P, et al. Emerging and re-emerging coronaviruses in pigs[J]. Curr Opin Virol, 2019, 34:39-49.
[4]	JUNG K, HU H, SAIF L J. Porcine deltacoronavirus infection:etiology, cell culture for virus isolation and propagation, molecular epidemiology and pathogenesis[J]. Virus Res, 2016, 226:50-59.
[5]	HUANG Y W, DICKERMAN A W, PIÑEYRO P, et al. Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States[J]. mBio, 2013, 4(5):e00737-13.
[6]	HU H, JUNG K, VLASOVA A N, et al. Experimental infection of gnotobiotic pigs with the cell-culture-adapted porcine deltacoronavirus strain OH-FD22[J]. Arch Virol, 2016, 161(12):3421-3434.
[7]	ZHANG H L, HAN F F, SHU X L, et al. Co-infection of porcine epidemic diarrhoea virus and porcine deltacoronavirus enhances the disease severity in piglets[J]. Transbound Emerg Dis, 2021, doi:10. 1111/tbed. 14144.
[8]	WOO P C Y, LAU S K P, LAM C S F, et al. Discovery of seven novel mammalian and avian coronaviruses in the genus Deltacoronavirus supports bat coronaviruses as the gene source of Alphacoronavirus and Betacoronavirus and avian coronaviruses as the gene source of Gammacoronavirus and Deltacoronavirus[J]. J Virol, 2012, 86(7):3995-4008.
[9]	WANG L Y, BYRUM B, ZHANG Y. Detection and genetic characterization of deltacoronavirus in pigs, Ohio, USA, 2014[J]. Emerg Infect Dis, 2014, 20(7):1227-1230.
[10]	JUNG K, HU H, EYERLY B, et al. Pathogenicity of 2 porcine deltacoronavirus strains in gnotobiotic pigs[J]. Emerg Infect Dis, 2015, 21(4):650-654.
[11]	CHEN Q, GAUGER P, STAFNE M, et al. Pathogenicity and pathogenesis of a United States porcine deltacoronavirus cell culture isolate in 5-day-old neonatal piglets[J]. Virology, 2015, 482:51-59.
[12]	JIN X H, ZHANG Y F, YUAN Y X, et al. Isolation, characterization and transcriptome analysis of porcine deltacoronavirus strain HNZK-02 from Henan province, China[J]. Mol Immunol, 2021, 134:86-99.
[13]	LEDNICKY J A, TAGLIAMONTE M S, WHITE S K, et al. Independent infections of porcine deltacoronavirus among Haitian children[J]. Nature, 2021, 600(7887):133-137.
[14]	WANG L, CHANG J J, VARGHESE D, et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth[J]. Nat Commun, 2013, 4:2035.
[15]	KIM M S, CHO H I, YOON H J, et al. JIB-04, a small molecule histone demethylase inhibitor, selectively targets colorectal cancer stem cells by inhibiting the Wnt/β-catenin signaling pathway[J]. Sci Rep, 2018, 8(1):6611.
[16]	ONER E, KOTMAKCI M, BAIRD A M, et al. Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids[J]. J Nanobiotechnol, 2021, 19(1):71.
[17]	BAYO J, FIORE E J, DOMINGUEZ L M, et al. A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets[J]. J Hepatol, 2019, 71(1):78-90.
[18]	TRAN T A, ZHANG Q J, WANG L, et al. Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival[J]. J Biol Chem, 2022, 298(2):101515.
[19]	SON J, HUANG S M, ZENG Q R, et al. JIB-04 has broad-spectrum antiviral activity and inhibits SARS-CoV-2 replication and coronavirus pathogenesis[J]. mBio, 2022, 13(1):e0337721.
[20]	FAN H H, QIAO L H, KANG K D, et al. Attachment and postattachment receptors important for hepatitis c virus infection and cell-to-cell transmission[J]. J Virol, 2017, 91(13):e00280-17.
[21]	JIANG J Y, CUN W, WU X F, et al. Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate[J]. J Virol, 2012, 86(13):7256-7267.
[22]	CUI X Y, WU Y H, FAN D Y, et al. Peptides P4 and P7 derived from E protein inhibit entry of dengue virus serotype 2 via interacting with β3 integrin[J]. Antiviral Res, 2018, 155:20-27.
[23]	LUO Z, KUANG X P, ZHOU Q Q, et al. Inhibitory effects of baicalein against herpes simplex virus type 1[J]. Acta Pharm Sin B, 2020, 10(12):2323-2338.
[24]	ZHANG H L, LIANG Q Q, LI B X, et al. Prevalence, phylogenetic and evolutionary analysis of porcine deltacoronavirus in Henan province, China[J]. Prev Vet Med, 2019, 166:8-15.
[25]	TANG R F, GUO L J, FAN Q J, et al. Porcine deltacoronavirus infection is inhibited by Griffithsin in cell culture[J]. Vet Microbiol, 2022, 264:109299.
[26]	CHU H F, CHEN C C, MOSES D C, et al. Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine[J]. Antiviral Res, 2018, 158:199-205.
[27]	MAGINNIS M S. Virus-receptor interactions:the key to cellular invasion[J]. J Mol Biol, 2018, 430(17):2590-2611.

Effects of Phenylpyridinone Derivative on the Replication of Porcine Deltacoronavirus

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 27

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	CHEN Shuyu, ZHU Xuejiao, ZHOU Jinzhu, TAO Ran, ZHANG Xuehan, Suolangsizhu, Gongga, LI Bin. Inhibition of Porcine Rotavirus in vitro Replication by Guanylate-binding Proteins GBP1 and GBP2 [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(1): 245-257.
[2]	WANG Ziyue, ZHANG Zihui, WU Wenxue, PENG Chen. Monkeypox: Diagnosis, Prevention and Treatments [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3195-3205.
[3]	WANG Zi, WANG Nianxiang, TIAN Changming, ZHAO Fujie, LIU Lintao, MA Mengyao, JIA Xinhao, LIU Guoxing, ZHENG Lanlan. Using Mouse to Evaluate the Immune Effect of Bridged Diphenylalanine Dipeptide with Inactivated Porcine Deltacoronavirus [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(4): 1590-1597.
[4]	LI Zhuowei, WANG Fang, WANG Junjun, CHEN Zhenhan, LI Huanrong, ZHOU Shuanghai, LIU Xuewei. Inhibitory Effect of Dicumarol on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1160-1168.
[5]	LIU Guang, GONG Chengyan, NIU Kaimin, ZHANG Shuo, TAO Deng, MA Jun, WU Xin, YIN Yulong, TANG Yulong. Study on Biological Activity of the Residue and Fermentation Products of Lianhua Qingwen [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1281-1299.
[6]	ZHUO Ruhao, LIU Qingyang, ZHONG Xiang. Advances in the Roles of Curcumin on Regulating Gut Microbiota and Antiviral Effects [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 473-483.
[7]	SUN Min, HAO Fei, ZHANG Wenwen, LI Wenliang, YANG Leilei, MAO Li, CHENG Zilong, LIU Maojun. The Antiviral Activity of Goat Interferon Alpha to Caprine Parainfluenza Virus 3 [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 736-743.
[8]	FAN Jinquan, ZHANG Yuhang, TANG Wuyang, ZHAO Xinyu, LI Pishun, ZHENG Xiaofeng. Inhibitory Effect of Decitabine on Porcine Circovirus Type 2 in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(12): 5134-5142.
[9]	CHEN Wenzhe, ZHANG Xiangle, GU Fengxing, ZHAO Zhenxiang, LI Kangli, XUE Zhaoning, ZHENG Haixue, ZHANG Xiaoli, ZHU Zixiang. Evaluation of the Antiviral Effect of Porcine GRK2 against Foot-and-mouth Disease Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4350-4361.
[10]	TANG Rongfeng, FAN Qianjin, GUO Longjun, ZHANG Xin, SHI Da, SHI Hongyan, CHEN Jianfei, FENG Li. Screening and Identification of Host Proteins Interacting with PDCoV S1-CTD [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(7): 2260-2267.
[11]	ZHAO Yujia, CHEN Rui, SONG Daili, ZHANG Luwen, XIAO Dai, LI Shiqian, WEN Yiping, WU Rui, ZHAO Qin, DU Senyan, YAN Qigui, WEN Xintian, CAO Sanjie, HUANG Xiaobo. Effect of Human Aminopeptidase N(hAPN) on Porcine Deltacoronavirus Infecting HEK293 Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(5): 1587-1597.
[12]	LIU Hejuan, SHI Chenxi, WANG Jing, WANG Meile, WANG Donghan, WEI Zhanyong, YIN Sugai. Exploration on the Potential Mechanism of Baicalein on Porcine Deltacoronavirus Infection Based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(11): 4097-4109.
[13]	SHI Xijuan, LIU Yuanzi, ZHANG Dajun, HOU Jing, SHEN Chaochao, YANG Bo, ZHANG Ting, YUAN Xingguo, REN Ruirui, DU Xiaohua, ZHANG Keshan, ZHENG Haixue, LIU Xiangtao. Porcine Cathepsin S Inhibits the Replication of Foot-and-Mouth Disease Virus Serotype O in PK-15 Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(6): 1652-1661.
[14]	ZHANG Hailing, LIAN Shizhen, ZHANG Dongliang, BAI Xue, ZHANG Shasha, ZHANG Lei, LI Wei, LIU Fangyuan, WANG Han, HU Bo, LU Shiying. Research Progress of Interferon-ε [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(11): 3023-3029.
[15]	ZHANG Xiaozhan, YANG Lei, DENG Tongwei, ZHAO Pandeng, PENG Zhifeng, CHEN Lulu, GUO Yiwen, XIA Yanxun, QIAO Hongxing, BIAN Chuanzhou, WANG Zeng. Development and Application of Recombinant Senecavirus A Expressing the Green Fluorescent Protein [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(10): 2978-2985.