双香豆素对猪繁殖与呼吸综合征病毒的体外抑制作用

doi:10.11843/j.issn.0366-6964.2023.03.027

Abstract

Abstract: In this study, we investigated the effect of dicumarol (DIC) on the proliferation of porcine reproductive and respiratory syndrome virus (PRRSV). Firstly, the cytotoxicity of DIC on Marc-145 cells was detected by CCK-8 method and calculated the half toxicity concentration (CC₅₀). Then, the effect of DIC on the proliferation of PRRSV was detected using qPCR and Western blot. Further, DIC targeted stage of PRRSV proliferation were explored by treating the cells with different administration methods. The results showed that the CC₅₀ of DIC against Marc-145 cells was 96.11 μmol·L^-1 and DIC exhibited significant anti-PRRSV activity at a concentration of 25 μmol·L^-1; DIC inhibited PRRSV proliferation in a dose-dependent manner at different times and titers. DIC had no effect on the adsorption, entry and release of the PRRSV infection cycle but significantly inhibited the replication of PRRSV. This study confirmed that DIC exhibited significant anti-PRRSV activity in Marc-145 cells at low concentrations and mainly targeted the replication phase of PRRSV, suggesting that DIC have the potential to be developed into clinical antiviral drugs or additives, providing a theoretical basis for the development of new PRRSV antiviral drugs.

Key words: dicumarol, porcine reproductive and respiratory syndrome virus, PRRSV, antiviral

CLC Number:

S852.659.6

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.

References 24

[1]	LUNNEY J K, FANG Y, LADINIG A, et al. Porcine reproductive and respiratory syndrome virus (PRRSV):pathogenesis and interaction with the immune system[J]. Annu Rev Anim Biosci, 2016, 4:129-154.
[2]	YIN B S, QI S S, SHA W L, et al. Molecular characterization of the Nsp2 and ORF5(ORF5a) genes of PRRSV strains in nine provinces of China during 2016-2018[J]. Front Vet Sci, 2021, 8:605832.
[3]	ZHAI S L, LIN T, ZHOU X, et al. Phylogeographic analysis of porcine reproductive and respiratory syndrome virus 1 in Guangdong province, Southern China[J]. Arch Virol, 2018, 163(9):2443-2449.
[4]	ZHU Z B, YUAN L L, HU D H, et al. Isolation and genomic characterization of a Chinese NADC34-like PRRSV isolated from Jiangsu province[J]. Transbound Emerg Dis, 2022, 69(4):e1015-e1027.
[5]	ZHANG Q Y, JIANG P, SONG Z B, et al. Pathogenicity and antigenicity of a novel NADC30-like strain of porcine reproductive and respiratory syndrome virus emerged in China[J]. Vet Microbiol, 2016, 197:93-101.
[6]	XIE C Z, WANG Z, HA Z, et al. Genetic characterization of a new NSP2-deletion porcine reproductive and Respiratory Syndrome Virus in China[J]. Microb Pathog, 2021, 150:104729.
[7]	AKRAM M, TAHIR I M, SHAH S M A, et al. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus:a systematic review[J]. Phytother Res, 2018, 32(5):811-822.
[8]	KARUPPANNAN A K, WU K X, QIANG J, et al. Natural compounds inhibiting the replication of Porcine reproductive and respiratory syndrome virus[J]. Antiviral Res, 2012, 94(2):188-194.
[9]	LIU X W, BAI J, JIANG C L, et al. Therapeutic effect of Xanthohumol against highly pathogenic porcine reproductive and respiratory syndrome viruses[J]. Vet Microbiol, 2019, 238:108431.
[10]	胡安君,毕亚楠,杨婉莉,等.甘草酸体外抗PRRSV的作用机制[J].中国兽医学报, 2018, 38(7):1386-1393.HU A J, BI Y N, YANG W L, et al. Mechanism of glycyrrhizic acid against PRRSV in vitro[J]. Chinese Journal of Veterinary Science, 2018, 38(7):1386-1393.(in Chinese)
[11]	HERNANDEZ A, LOÓPEZ-LLUCH G, BERNAL J A, et al. Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition of Hsp90[J]. Mol Cancer Ther, 2008, 7(3):474-482.
[12]	魏静,冯跃平,郑茜,等.双香豆素体外抗肿瘤活性筛选及相关机制初探[J].药学学报, 2020, 55(12):2904-2910.WEI J, FENG Y P, ZHENG X, et al. Anti-tumor activity screening and research on the primary mechanism of dicumarol in vitro[J]. Acta Pharmaceutica Sinica, 2020, 55(12):2904-2910.(in Chinese)
[13]	CHEN C H, HSIEH Y C, YANG P M, et al. Dicoumarol suppresses HMGA2-mediated oncogenic capacities and inhibits cell proliferation by inducing apoptosis in colon cancer[J]. Biochem Res Commun, 2020, 524(4):1003-1009.
[14]	CHENG S T, HU J L, REN J H, et al. Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx[J]. J Hepatol, 2021, 74(3):522-534.
[15]	LIVAK K J, SCHMITTGEN T D. Analysis of relative gene expression data using real-time quantitative PCR and the method[J]. Methods, 2001, 25(4):402-408.
[16]	SCORTTI M, PRIETO C,ÁLVAREZ E, et al. Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV[J]. Vet Rec, 2007, 161(24):809-813.
[17]	ROSE N, RENSON P, ANDRAUD M, et al. Porcine reproductive and respiratory syndrome virus (PRRSv) modified-live vaccine reduces virus transmission in experimental conditions[J]. Vaccine, 2015, 33(21):2493-2499.
[18]	HOLTKAMP D J, KLIEBENSTEIN J B, NEUMANN E J, et al. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers[J]. J Swine Health Prod, 2013, 21(2):72-84.
[19]	KHATUN A, SHABIR N, SEO B J, et al. The attenuation phenotype of a ribavirin-resistant porcine reproductive and respiratory syndrome virus is maintained during sequential passages in pigs[J]. J Virol, 2016, 90(9):4454-4468.
[20]	BEN-SHABAT S, YARMOLINSKY L, PORAT D, et al. Antiviral effect of phytochemicals from medicinal plants:applications and drug delivery strategies[J]. Drug Deliv Trans Res, 2020, 10(2):354-367.
[21]	SUN C, ZHAO W W, WANG X M, et al. A pharmacological review of dicoumarol:an old natural anticoagulant agent[J]. Pharmacol Res, 2020, 160:105193.
[22]	WISHART J H, CHAPMAN C B. Dicumarol therapy in congestive heart failure[J]. N Engl J Med, 1948, 239(19):701-704.
[23]	徐梦娴,李明凯,涂忠忠,等.香豆素化合物体内外抗狂犬病病毒的效果[J].中国兽医学报, 2019, 39(2):250-259.XU M X, LI M K, TU Z Z, et al. Inhibition of rabies virus by coumarin in vitro and in vivo[J]. Chinese Journal of Veterinary Science, 2019, 39(2):250-259.(in Chinese)
[24]	陈绪林,安利伟.双香豆素在制备治疗或预防流感病毒感染的药物中的应用:中国, 103720687A[P]. 2014-04-16.CHEN X L, AN L W. Application of bicoumarins in the preparation of drugs for the treatment or prevention of influenza virus infection:CN, 103720687A[P]. 2014-04-16.(in Chinese)

Inhibitory Effect of Dicumarol on Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in vitro

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