体外对猪流行性腹泻病毒复制具有抑制效应的物质

doi:10.11843/j.issn.0366-6964.2025.06.005

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (6): 2577-2589.doi: 10.11843/j.issn.0366-6964.2025.06.005

体外对猪流行性腹泻病毒复制具有抑制效应的物质

王运珂¹^,²^,³^,⁴(), 王娜¹^,²^,³^,⁴^,*(), 岳珂¹^,²^,³^,⁴, 何坤淼¹^,²^,³^,⁴, 张兴¹^,²^,³^,⁴, 刘垚¹^,²^,³^,⁴, 张改平¹^,²^,³^,*()

1. 河南农业大学动物医学院，郑州 450046
2. 动物免疫学国际联合研究中心，郑州 450046
3. 龙湖现代免疫实验室，郑州 450046
4. 郑州市营养与健康食品重点实验室，郑州 450002

收稿日期:2024-07-29 出版日期:2025-06-23 发布日期:2025-06-25
通讯作者: 王娜,张改平 E-mail:wangyunke2000@163.com;na-wang@163.com;zhanggaip@126.com
作者简介:王运珂(2000-)，女，河南新乡人，硕士生，主要从事预防兽医学研究，E-mail: wangyunke2000@163.com
基金资助:
河南省重大科技专项项目(221100110600)

Substances with Inhibitory Effects on Porcine Epidemic Diarrhea Virus Replication in vitro

WANG Yunke¹^,²^,³^,⁴(), WANG Na¹^,²^,³^,⁴^,*(), YUE Ke¹^,²^,³^,⁴, HE Kunmiao¹^,²^,³^,⁴, ZHANG Xing¹^,²^,³^,⁴, LIU Yao¹^,²^,³^,⁴, ZHANG Gaiping¹^,²^,³^,*()

1. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China
2. International Joint Research Center of National Animal lmmunology, Zhengzhou 450046, China
3. Longhu Laboratory, Zhengzhou 450046, China
4. Zhengzhou Key Laboratory of Nutrition and Health Food, Zhengzhou 450002, China

Received:2024-07-29 Online:2025-06-23 Published:2025-06-25
Contact: WANG Na, ZHANG Gaiping E-mail:wangyunke2000@163.com;na-wang@163.com;zhanggaip@126.com

摘要/Abstract

摘要：

猪流行性腹泻病毒(porcine epidemic diarrhea virus，PEDV)是一种引起仔猪急性腹泻、呕吐、脱水等症状的病毒，由于其高发病率和高致死率，给全球养猪业造成了巨大的经济损失。虽然疫苗接种是当前预防猪流行性腹泻(porcine epidemic diarrhea, PED)最经济和有效的措施，但PEDV变异株的频繁出现使得现有疫苗的免疫保护效果不佳，因此开发有效的抗病毒药物显得尤为迫切。近年来，研究者致力于筛选和评估具有潜在抗PEDV活性的物质，其主要通过靶向病毒的入侵、复制或装配过程，或通过增强宿主的免疫响应来发挥作用。本文从化学药物、天然产物和其他生物制剂抗PEDV作用及机制进行概述，以期为抗PEDV药物的筛选和研究提供新的方向和思路。

关键词: 猪流行性腹泻病毒, 化学药物, 天然产物, 生物制剂

Abstract:

Porcine epidemic diarrhea virus (PEDV) is a virus that causes acute diarrhea, vomiting, dehydration, and other symptoms in piglets. Due to its high incidence rate and high mortality, it has caused substantial economic losses to the global pig industry. Although vaccination is currently the most economical and effective measure for preventing porcine epidemic diarrhea (PED), the frequent emergence of PEDV variants has resulted in poor immune protection from existing vaccines, making the development of effective antiviral drugs particularly urgent. In recent years, researchers have been dedicated to screening and evaluating substances with potential anti-PEDV activity, which mainly exert their effects by targeting the invasion, replication, or assembly processes of the virus, or by enhancing the host's immune response. This article provides an overview of the anti-PEDV effects and mechanisms of chemical drugs, natural products, and other biological agents, in order to provide new directions and ideas for the screening and research of anti-PEDV drugs.

Key words: porcine epidemic diarrhea virus, chemical drugs, natural products, biological agents

中图分类号:

S852.659.6

王运珂, 王娜, 岳珂, 何坤淼, 张兴, 刘垚, 张改平. 体外对猪流行性腹泻病毒复制具有抑制效应的物质[J]. 畜牧兽医学报, 2025, 56(6): 2577-2589.

WANG Yunke, WANG Na, YUE Ke, HE Kunmiao, ZHANG Xing, LIU Yao, ZHANG Gaiping. Substances with Inhibitory Effects on Porcine Epidemic Diarrhea Virus Replication in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(6): 2577-2589.

图/表 3

表 1

表 2

基于体内外模型的抗PEDV感染天然产物"

天然产物 Natural products	主要来源 Main source	分类 Classification	作用机制 Mechanism	参考文献 Reference
槲皮素 Quercetin	洋葱、西红柿、葡萄等	黄酮类	下调NF-κB信号和炎症因子水平；缓解PEDV引起的临床症状和肠道损伤；提高抗氧化能力	[27-29]
金丝桃苷 Hyperoside	山楂	黄酮类	抑制PEDV N和p53蛋白相互作用	[30]
葛根素 Puerarin	葛根	黄酮类	调节干扰素信号通路；抑制NF-κB通路；缓解PEDV感染引起的氧化应激	[31-33]
姜黄素 Curcumin	姜黄	黄酮类	增强Vero细胞抗病毒细胞因子	[34]
汉黄芩素 Wogonin	黄芩	黄酮类	抑制PEDV的进入、复制和释放阶段；体外直接灭活PEDV；抑制PEDV 3CLpro活性	[36]
黄芩苷 Baicalin	黄芩	黄酮类	抑制PEDV 3CLpro；抑制PEDV早期复制阶段	[37]
黄芩素 Baicalein	黄芩	黄酮类	抑制PEDV 3CLpro；抑制PEDV早期复制阶段；抑制PEDV吸附或进入阶段	[37]
木犀草素 Luteolin	金银花、菊花等	黄酮类	抑制PEDV 3CLpro；抑制PEDV进入、复制及释放阶段；抑制促炎细胞因子的产生	[38]
鞣花酸 Ellagic acid	桃金娘	酚酸类	改善PEDV感染导致的仔猪氧化应激和蛋白合成代谢紊乱；激活相关的干扰素途径	[39-41]
白藜芦醇 Resveratrol	桃金娘	酚酸类	抑制PEDV的复制	[39]
没食子酸 Gallic acid	桃金娘	酚酸类	抑制PEDV的复制	[39]
白皮杉醇 Piceatannol	桃金娘	酚酸类	抑制PEDV的复制	[39]
三乙酰白藜芦醇 Triacetyl resveratrol	虎杖、葡萄	酚酸类	诱导PEDV感染细胞的早期凋亡；激活线粒体相关的caspase途径	[42]
单宁酸 Tannic acid	五倍子、高粱、石榴等	酚酸类	抑制PEDV的吸附或入侵阶段；抑PEDV 3CLpro；改善肠道损伤；提高抗氧化能力	[43, 44]
没食子酸辛酯 Octyl gallate	茶叶、葡萄籽等	酚酸类	抑制PEDV 3CLpro；缓解PEDV引起的临床症状和肠道损伤	[45]
咔唑生物碱衍生物 Carbazole alkaloid derivatives	煤焦油和芸香科植物	生物碱	抑制PEDV的吸附阶段	[46]
苦参碱 Matrine	苦参	生物碱	抑制PEDV吸附和进入阶段；直接杀灭病毒粒子；激活MAPK信号通路促进细胞凋亡	[47]
去氢吴茱萸碱 Dehydroevodiamine	吴茱萸	生物碱	抑制PEDV的复制阶段；下调ERK1/2和MAPK通路	[48]
藜芦碱 Veratramine	藜芦	生物碱	抑制PEDV的进入阶段；抑制巨胞饮作用	[49]
益智果多糖3 Alpiniae oxyphyllae fructus polysaccharide 3	益智果	多糖类	抑制PEDV的进入阶段；降低胆固醇水平	[50]
马齿苋多糖 Portulaca oleracea polysaccharide	马齿苋	多糖类	抑制PEDV的吸附阶段；降低细胞因子IFN-α、TNF-α和IL-6蛋白含量	[51]
银杏叶外果皮多糖 Polysaccharide from Ginkgo biloba exocarp	银杏叶外果皮	多糖类	抑制PEDV的吸附和进入阶段；直接灭活PEDV粒子	[52]
胞外多糖 Extracellular polysaccharide	乳酸杆菌	多糖类	激活IFN-λ的表达；抑制PEDV的复制及其引发的炎症反应	[53]
茯苓多糖 Poria cocos polysaccharides	茯苓	多糖类	缓解炎性反应；缓解肠道损伤	[54]
甘草酸 Glycyrrhizin	甘草	萜类	通过HMGB1/TLR4-MAPK p38途径抑制PEDV感染；降低促炎细胞因子的表达水平	[55]
三萜类化合物6，9，11，13 Oleanane triterpenes 6，9，11，13	山茶花	萜类	抑制PEDV多个关键基因和蛋白质的合成	[56]
欧当归内酯A Levistolide A	川芎	丁基苯酞类	抑制PEDV的吸附和入侵阶段；诱导ROS的产生	[57]
月桂酸甘油酯 Monolaurin	椰子油和人母乳	脂肪酸	改善肠道功能；降低促炎细胞因子的表达；调节干扰素途径	[58]
蒲公英提取物 Dandelion extract	蒲公英	-	抑制PEDV的复制	[59]
黄芩提取物 Scutellaria baicalensis extract	黄芩	-	抑制PEDV的复制	[59]
金丝桃提取物 Hypericum japonicum extract	金丝桃	-	抑制PEDV的复制阶段；调节肠道菌群	[60]
泽漆水提取物 Euphorbia helioscopia water extract	泽漆	-	抑制PEDV的吸附和复制阶段	[61]
芦荟提取物 Aloe extract	芦荟	-	抑制PEDV的复制阶段；直接杀灭病毒粒子	[62]
甘草提取物 Licorice extract	甘草	-	抑制了病毒的吸附、入侵和复制阶段；缓解肠道病理损伤	[63]
马齿苋提取物 Portulaca oleracea L. extracts	马齿苋		下调细胞因子水平；抑制NF-κB信号通路	[64]
白头翁散煎剂发酵物 Fermented pulsatilla decoctio	-	-	加强肠道屏障功能；调整肠道微生态	[65]
理中汤 Lizhong decoction	-	-	减少细胞凋亡；缓解肠道病理损伤	[66]

表 2

图 1

参考文献 76

1	LEIDENBERGER S , SCHRODER C , ZANI L , et al. Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies[J]. Sci Rep, 2017, 7 (1): 10825. doi: 10.1038/s41598-017-11160-w
2	JUNG K , SAIF L J , WANG Q . Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control[J]. Virus Res, 2020, 286, 198045. doi: 10.1016/j.virusres.2020.198045
3	LI Y , WU Q , HUANG L , et al. An alternative pathway of enteric PEDV dissemination from nasal cavity to intestinal mucosa in swine[J]. Nat Comm, 2018, 9 (1): 3811. doi: 10.1038/s41467-018-06056-w
4	LI M , PAN Y , XI Y , et al. Insights and progress on epidemic characteristics, genotyping, and preventive measures of PEDV in China: A review[J]. Microbl Pathogenesis, 2023, 181, 106185. doi: 10.1016/j.micpath.2023.106185
5	XU X , DU L , FAN B , et al. A flagellin-adjuvanted inactivated porcine epidemic diarrhea virus (PEDV) vaccine provides enhanced immune protection against PEDV challenge in piglets[J]. Arch Virol, 2020, 165 (6): 1299- 1309. doi: 10.1007/s00705-020-04567-w
6	YUAN C , HUANG X , ZHAI R , et al. In vitro antiviral activities of salinomycin on porcine epidemic diarrhea virus[J]. Viruses, 2021, 13 (4): 580. doi: 10.3390/v13040580
7	马亚娟, 苏恺, 林依丹, 等. 盐霉素体外对猪流行性腹泻病毒的抑制效果[J]. 畜牧兽医学报, 2024, 55 (4): 1661- 1671.
	MA Y J , SU K , LIN Y D , et al. In vitro inhibitory effect of monensin on porcine epidemic diarrhea virus[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55 (4): 1661- 1671.
8	赵普, 陈欢, 张财盛, 等. 两性霉素B对猪流行性腹泻病毒入胞的抑制作用研究[J]. 畜牧与兽医, 2023, 55 (2): 73- 79.
	ZHAO P , CHEN H , ZHANG C S , et al. Inhibitory effect of amphotericin B on porcine epidemic diarrhea virus entry[J]. Animal Husbandry and Veterinary Medicine, 2023, 55 (2): 73- 79.
9	詹晶. 松萝酸对PEDV复制的影响及PEDV的细胞培养遗传稳定性分析[D]. 南京: 南京农业大学, 2020.
	ZHAN J. Effects of usnic acid on PEDV replication and genetic stability analysis of PEDV in cell culture[D]. Nanjing: Nanjing Agricultural University, 2020. (in Chinese)
10	WANG Y , QIN P , ZHAO C , et al. Evaluating anti-viral effect of ivermectin on porcine epidemic diarrhea virus and analyzing the related genes and signaling pathway by RNA-seq in vitro[J]. Virology, 2023, 587, 109877. doi: 10.1016/j.virol.2023.109877
11	魏秉洁, 张翠玲, 尚超, 等. 巴弗洛霉素A1体外广谱抗冠状病毒作用研究[J]. 中国病原生物学杂志, 2023, 18 (3): 260-264, 270.
	WEI B J , ZHANG C L , SHANG C , et al. In vitro broad-spectrum antiviral activity of bafilomycin A1 against coronaviruses[J]. Chinese Journal of Pathogen Biology, 2023, 18 (3): 260-264, 270.
12	WEI R , LI L , CHEN H , et al. Inhibition of porcine reproductive and respiratory syndrome virus replication by rifampicin in vitro[J]. Front Vet Sci, 2024, 11, 1439015. doi: 10.3389/fvets.2024.1439015
13	RAMASWAMY K , RASHID M , RAMASAMY S , et al. Revisiting viral RNA-dependent RNA polymerases: Insights from recent structural studies[J]. Viruses, 2022, 14 (10): 2200. doi: 10.3390/v14102200
14	王一铭, 刘建波, 冯力. 瑞德西韦在体外抑制猪流行性腹泻病毒复制的研究[J]. 中国预防兽医学报, 2022, 44 (8): 810- 816.
	WANG Y M , LIU J B , FENG L . In vitro inhibitory effect of remdesivir on porcine epidemic diarrhea virus replication[J]. Chinese Journal of Preventive Veterinary Medicine, 2022, 44 (8): 810- 816.
15	HUANG Z X , ZHOU S T , WANG J , et al. Remdesivir inhibits porcine epidemic diarrhea virus infection in vitro[J]. Heliyon, 2023, 9 (11): e21468.. doi: 10.1016/j.heliyon.2023.e21468
16	BARNARD D L , HUBBARD V D , BURTON J , et al. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-D-N4-hydroxycytidine[J]. Antiviral Chem Chemother, 2004, 15 (1): 15- 22. doi: 10.1177/095632020401500102
17	TOOTS M , YOON J J , COX R M , et al. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia[J]. Sci Transl Med, 2019, 11 (515): eaax5866. doi: 10.1126/scitranslmed.aax5866
18	HUANG Z X , ZHOU S T , YANG Z B , et al. Molnupiravir inhibits porcine epidemic diarrhea virus infection in vitro[J]. Viruses, 2023, 15 (6): 1317. doi: 10.3390/v15061317
19	LI M , ZHANG L , PAN L , et al. Nicotinamide efficiently suppresses porcine epidemic diarrhea virus and porcine deltacoronavirus replication[J]. Viruses, 2023, 15 (7): 1591. doi: 10.3390/v15071591
20	YANG J , TIAN G , CHEN D , et al. 1, 25-dihydroxyvitamin D(3) inhibits porcine epidemic diarrhea virus replication by regulating cell cycle resumption in IPEC-J2 porcine epithelial cells[J]. Microb Pathogenesis, 2021, 158, 105017. doi: 10.1016/j.micpath.2021.105017
21	YANG J , CHEN D , TIAN G , et al. 1, 25-dihydroxyvitamin D(3) negatively regulates the inflammatory response to porcine epidemic diarrhea virus infection by inhibiting NF-kappaB and JAK/STAT signaling pathway in IPEC-J2 porcine epithelial cells[J]. Int J Mol Sci, 2022, 23 (18): 10603. doi: 10.3390/ijms231810603
22	REN J , ZENG W , JIANG C , et al. Inhibition of porcine epidemic diarrhea virus by cinchonine via inducing cellular autophagy[J]. Front Cell Infect Microbiol, 2022, 12, 856711. doi: 10.3389/fcimb.2022.856711
23	张财盛, 陈欢, 司安琪, 等. 依福地平对猪流行性腹泻病毒的抑制作用研究[J]. 畜牧与兽医, 2024, 56 (3): 62- 68.
	ZHANG C S , CHEN H , SI A Q , et al. Inhibitory effect of ifenprodil on porcine epidemic diarrhea virus[J]. Animal Husbandry and Veterinary Medicine, 2024, 56 (3): 62- 68.
24	LI H J , GAO D S , LI Y T , et al. Antiviral effect of lithium chloride on porcine epidemic diarrhea virus in vitro[J]. Res Vet Sci, 2018, 118, 288- 294.
25	WANG Y , HUANG H , LI D , et al. Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization[J]. Virol Sin, 2023, 38 (2): 296- 308.
26	牛晓雨, 邢媛媛, 李大彪. 植物活性成分对动物肠道屏障功能的调控作用及其机制[J]. 畜牧兽医学报, 2024, 55 (4): 1467- 1477.
	NIU X Y , XING Y Y , LI D B . Regulation and mechanism of plant bioactive components on animal intestinal barrier function[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55 (4): 1467- 1477.
27	GONG T , WU D , FENG Y , et al. Inhibitory effects of quercetin on porcine epidemic diarrhea virus in vitro and in vivo[J]. Virology, 2024, 589, 109923.
28	王帅杰, 谭子涵, 李晗博, 等. 槲皮素对PEDV感染幼龄仔猪肠道形态、抗氧化功能及空肠脂质代谢基因表达的影响[J]. 中国畜牧兽医, 2022, 49 (9): 3391- 3399.
	WANG S J , TAN Z H , LI H B , et al. Effects of quercetin on intestinal morphology, antioxidant function, and jejunal lipid metabolism gene expression in PEDV-infected weaned piglets[J]. Chinese Journal of Animal Husbandry and Veterinary Science, 2022, 49 (9): 3391- 3399.
29	汪曼丽, 谭子涵, 王帅杰, 等. 槲皮素对PEDV感染幼龄仔猪的生长性能、血液生化指标和肠道吸收与屏障功能的影响[J]. 中国畜牧兽医, 2022, 49 (9): 3411- 3418.
	WANG M L , TAN Z H , WANG S J , et al. Effects of quercetin on growth performance, blood biochemical indices, and intestinal absorption and barrier function in PEDV-infected weaned piglets[J]. Chinese Journal of Animal Husbandry and Veterinary Science, 2022, 49 (9): 3411- 3418.
30	WANG J , SUN H , SU M , et al. Natural hyperoside extracted from hawthorn exhibits antiviral activity against porcine epidemic diarrhea virus in vitro and in vivo[J]. Virology, 2024, 594, 110037.
31	孙海波. 山楂中金丝桃苷提取及其抗猪流行性腹泻病毒作用研究[D]. 大庆: 黑龙江八一农垦大学, 2023.
	SUN H B. Extraction of hyperoside from hawthorn and its antiviral activity against porcine epidemic diarrhea virus[D]. Daqing: Heilongjiang Bayi Agricultural University, 2023. (in Chinese)
32	WU M , ZHANG Q , YI D , et al. Quantitative proteomic analysis reveals antiviral and anti-inflammatory effects of puerarin in piglets infected with porcine epidemic diarrhea virus[J]. Front Immunol, 2020, 11, 169.
33	胡玉妍, 王倩, 谌梦, 等. 葛根素对PEDV感染幼龄仔猪肺脏、脾脏和肠系膜淋巴结抗氧化功能和免疫功能的影响[J]. 中国畜牧杂志, 2024, 60 (2): 383- 390.
	HU Y Y , WANG Q , CHEN M , et al. Effects of puerarin on antioxidant and immune functions in the lungs, spleen, and mesenteric lymph nodes of PEDV-infected weaned piglets[J]. Chinese Journal of Animal Husbandry, 2024, 60 (2): 383- 390.
34	刘向阳, 周扬, 张淑娟, 等. 姜黄素抑制PEDV感染Vero细胞的作用研究[J]. 中国兽医科学, 2023, 53 (5): 641- 648.
	LIU X Y , ZHOU Y , ZHANG S J , et al. Inhibitory effect of curcumin on PEDV infection in Vero cells[J]. Chinese Journal of Veterinary Science, 2023, 53 (5): 641- 648.
35	JO S , KIM S , SHIN D H , et al. Inhibition of SARS-CoV 3CL protease by flavonoids[J]. J Enzym Inhib Med Chem, 2020, 35 (1): 145- 151.
36	WANG J , ZENG X , YIN D , et al. In silico and in vitro evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus[J]. Front Cell Infect Microbiol, 2023, 13, 1123650.
37	LI Z , ZHU L , WANG L , et al. Identification of two flavonoids antiviral inhibitors targeting 3C-like protease of porcine epidemic diarrhea virus[J]. Front Microbiol, 2024, 15, 1357470.
38	WANG J , ZENG X , GOU J , et al. Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro[J]. BMC Vet Res, 2024, 20 (1): 288.
39	刘伟, 银慧慧, 赵武, 等. 桃金娘4种酚类成分体外抗猪流行性腹泻病毒活性研究[J]. 现代畜牧兽医, 2020 (6): 11- 13.
	LIU W , YIN H H , ZHAO W , et al. In vitro antiviral activity of four phenolic compounds from Myrtle against porcine epidemic diarrhea virus[J]. Modern Animal Husbandry and Veterinary Medicine, 2020 (6): 11- 13.
40	陈嵚崟, 邓翠芳, 臧佳佳, 等. 鞣花酸对猪流行性腹泻病毒感染仔猪生长性能、血液生化指标和抗氧化功能的影响[J]. 中国畜牧杂志, 2024, 60 (3): 235-239, 246.
	CHEN Q Y , DENG C F , ZANG J J , et al. Effects of ellagic acid on growth performance, blood biochemical indices, and antioxidant function in PEDV-infected weaned piglets[J]. Chinese Journal of Animal Husbandry, 2024, 60 (3): 235-239, 246.
41	SONG Z , DENG C , CHEN Q , et al. Protective effects and mechanisms of ellagic acid on intestinal injury in piglets infected with porcine epidemic diarrhea virus[J]. Front Immunol, 2024, 15, 1323866.
42	WANG X , LIU Y , LI K , et al. Triacetyl resveratrol inhibits PEDV by inducing the early apoptosis in vitro[J]. Int J Mol Sci, 2022, 23 (23): 14499.
43	曾一桐, 朱靓芸, 童庆芳, 等. 单宁酸对猪流行性腹泻病毒增殖的体外抑制作用[J]. 中国畜牧兽医, 2023, 50 (10): 4150- 4159.
	ZENG Y T , ZHU L Y , TONG Q F , et al. Inhibitory effect of tannic acid on PEDV proliferation in vitro[J]. Chinese Journal of Animal Husbandry and Veterinary Science, 2023, 50 (10): 4150- 4159.
44	王思甜, 徐朋涛, 郑丽云, 等. 单宁酸对感染猪流行性腹泻病毒仔猪生长性能、肠道屏障功能和抗氧化能力的影响[J]. 动物营养学报, 2023, 35 (7): 4276- 4286.
	WANG S T , XU P T , ZHENG L Y , et al. Effects of tannic acid on growth performance, intestinal barrier function, and antioxidant capacity in PEDV-infected weaned piglets[J]. Journal of Animal Nutrition, 2023, 35 (7): 4276- 4286.
45	SU M , YIN B , XING X , et al. Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV[J]. Vet Microbiol, 2023, 281, 109743.
46	陈金凤. 咔唑生物碱衍生物对猪流行性腹泻病毒复制的抑制作用[D]. 南昌: 江西农业大学, 2023.
	CHEN J F. Inhibitory effect of carbazole alkaloid derivatives on PEDV replication[D]. Nanchang: Jiangxi Agricultural University, 2023. (in Chinese)
47	QIAO W T , YAO X , LU W H , et al. Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway[J]. Int J Biol Macromol, 2024, 270 (Pt 2): 132408.
48	LI K , WANG H , CHEN T , et al. Dehydroevodiamine inhibits PEDV through regulateing ERK1/2 MAPK pathway in Vero cells[J]. Virology, 2024, 598, 110166.
49	CHEN H , ZHAO P , ZHANG C , et al. Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway[J]. Virus Res, 2024, 339, 199260.
50	LUO Q , ZHANG C , CHEN Y , et al. Alpiniae oxyphyllae fructus polysaccharide 3 inhibits porcine epidemic diarrhea virus entry into IPEC-J2 cells[J]. Res Vet Sci, 2022, 152, 434- 441.
51	赵鲁, 刘月月, 林树乾, 等. 马齿苋多糖对猪流行性腹泻病毒抑制作用的研究[J]. 中国兽医科学, 2020, 50 (08): 1066- 1072.
	ZHAO L , LIU Y Y , LIN S Q , et al. Study on the inhibitory effect of Portulaca oleracea polysaccharide on porcine epidemic diarrhea virus[J]. Chinese Journal of Veterinary Science, 2020, 50 (8): 1066- 1072.
52	LEE J H , PARK J S , LEE S W , et al. Porcine epidemic diarrhea virus infection: inhibition by polysaccharide from Ginkgo biloba exocarp and mode of its action[J]. Virus Res, 2015, 195, 148- 152.
53	CHEN S , NAI Z , QIN Z , et al. The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus[J]. Microb Cell Fact, 2023, 22 (1): 225.
54	谌梦, 胡锦超, 田晓榕, 等. 葛根素与茯苓多糖复合物对PEDV感染幼龄仔猪结肠的保护作用[J]. 饲料工业, 2024, 45 (16): 47- 54.
	CHEN M , HU J C , TIAN X R , et al. Protective effect of a combination of Puerarin and Poria cocos polysaccharides on PEDV-infected young piglets[J]. Feed Industry, 2024, 45 (16): 47- 54.
55	GAO R , ZHANG Y , KANG Y , et al. Glycyrrhizin inhibits PEDV infection and proinflammatory cytokine secretion via the HMGB1/TLR4-MAPK p38 pathway[J]. Int J Mol Sci, 2020, 21 (8): 2961.
56	YANG J L , HA T K , DHODARY B , et al. Oleanane triterpenes from the flowers of Camellia japonica inhibit porcine epidemic diarrhea virus (PEDV) replication[J]. J Med Chem, 2015, 58 (3): 1268- 1280.
57	ZENG W , REN J , LI Z , et al. Levistolide A inhibits PEDV replication via inducing ROS generation[J]. Viruses, 2022, 14 (2): 258.
58	ZHANG Q , YI D , JI C , et al. Monolaurin confers a protective effect against porcine epidemic diarrhea virus infection in piglets by regulating the interferon pathway[J]. Front Immunol, 2021, 12, 797476.
59	甘晓凤, 孟心茹, 郭丽君, 等. 几种中药体外抗猪流行性腹泻病毒活性的研究[J]. 中国预防兽医学报, 2024, 46 (3): 229- 235.
	GAN X F , MENG X R , GUO L J , et al. In vitro antiviral activity of several Chinese herbal medicines against porcine epidemic diarrhea virus[J]. Chinese Journal of Preventive Veterinary Medicine, 2024, 46 (3): 229- 235.
60	RAO H , SU W , ZHANG X , et al. Hypericum japonicum extract inhibited porcine epidemic diarrhea virus in vitro and in vivo[J]. Front Pharmacol, 2023, 14, 1112610.
61	钟睦琪, 李凯远, 王雪, 等. 泽漆水提取物对猪流行性腹泻病毒的体外抑制作用研究[J]. 中国农业大学学报, 2023, 28 (10): 132- 140.
	ZHONG M Q , LI K Y , WANG X , et al. In vitro inhibitory effect of Euphorbia helioscopia water extract on porcine epidemic diarrhea virus[J]. Journal of China Agricultural University, 2023, 28 (10): 132- 140.
62	XU Z , LIU Y , PENG P , et al. Aloe extract inhibits porcine epidemic diarrhea virus in vitro and in vivo[J]. Vet Microbiol, 2020, 249, 108849.
63	BAI W , ZHU Q , WANG J , et al. Licorice extract inhibits porcine epidemic diarrhea virus in vitro and in vivo[J]. J Gen Virol, 2024, 105 (3): 001964.
64	LIU Y , ZHAO L , XIE Y , et al. Antiviral activity of Portulaca oleracea L. extracts against porcine epidemic diarrhea virus by partial suppression on myd88/NF-kappaB activation in vitro[J]. Microb Pathog, 2021, 154, 104832.
65	常伟辰, 李帅奇, 李琰, 等. 白头翁散煎剂发酵物对感染猪流行性腹泻病毒仔猪肠道屏障功能的影响[J]. 畜牧兽医学报, 2023, 54 (10): 4403- 4410. doi: 10.11843/j.issn.0366-6964.2023.10.036
	CHANG W C , LI S Q , LI Y , et al. Effects of fermented pulsatilla decoction on intestinal barrier function in PEDV-infected weaned piglets[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54 (10): 4403- 4410. doi: 10.11843/j.issn.0366-6964.2023.10.036
66	CHEN X , CHEN X , QU Q , et al. Lizhong decoction inhibits porcine epidemic diarrhea virus in vitro and in vivo[J]. J Ethnopharmacol, 2024, 333, 118428.
67	张弘石. 重组猪干扰素的制备及其体外抗PEDV活性的分析[D]. 扬州: 扬州大学, 2023.
	ZHANG H S. Preparation of recombinant porcine interferon and analysis of its antiviral activity against PEDV[D]. Yangzhou: Yangzhou University, 2023. (in Chinese)
68	朱睿, 张弘石, 吴植, 等. 猪干扰素α的原核可溶性表达及抗PEDV活性[J]. 中国兽医学报, 2024, 44 (3): 550- 557.
	ZHU R , ZHANG H S , WU Z , et al. Soluble expression of porcine interferon α and its antiviral activity against PEDV[J]. Chinese Journal of Veterinary Science, 2024, 44 (03): 550- 557.
69	宋诗莹, 郭玮璐, 夏学峰, 等. 猪IFN-δ5的表达纯化及其抗PEDV感染的作用分析[J]. 中国畜牧兽医, 2022, 49 (8): 3171- 3179.
	SONG S Y , GUO W L , XIA X F , et al. Expression purification of porcine IFN-δ5 and analysis of its antiviral activity against PEDV infection[J]. Chinese Journal of Animal Husbandry and Veterinary Science, 2022, 49 (8): 3171- 3179.
70	GONG L , LIN Y , QIN J , et al. Neutralizing antibodies against porcine epidemic diarrhea virus block virus attachment and internalization[J]. Virology Journal, 2018, 15 (1): 133.
71	高玉, 葛旭影, 曹丽艳, 等. 猪流行性腹泻病毒M蛋白亲和肽的筛选及其抗病毒作用[J]. 中国兽医科学, 2015, 45 (07): 674- 679.
	GAO Y , GE X Y , CAO L Y , et al. Screening of affinity peptides for PEDV M protein and their antiviral activity[J]. Chinese Journal of Veterinary Science, 2015, 45 (07): 674- 679.
72	郝峰. 抗PoRV和PEDV二联卵黄抗体的研制及初步应用[D]. 咸阳: 西北农林科技大学, 2023.
	HAO F. Development and preliminary application of dual anti-PoRV and PEDV yolk antibodies [D]. Xianyang: Northwest A & F University, 2023. (in Chinese)
73	邱存义. 融合表达PEDV S蛋白抗原区与IFN-γ重组腺病毒的构建及卵黄抗体制备与免疫效果评价[D]. 咸阳: 西北农林科技大学, 2023.
	QIU C Y. Construction of recombinant adenovirus expressing PEDV S protein antigen region and IFN-γ and preparation and evaluation of immune efficacy of yolk antibodies[D]. Xianyang: Northwest A & F University, 2023. (in Chinese)
74	LEE D H , JEON Y S , PARK C K , et al. Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets[J]. Arch Virol, 2015, 160 (9): 2197- 2207.
75	丁雨善. 猪流行性腹泻病毒(PEDV)卵黄抗体的研制[D]. 南阳: 南阳师范学院, 2020.
	DING Y S. Development of yolk antibodies against porcine epidemic diarrhea virus (PEDV)[D]. Nanyang: Nanyang Normal University, 2020. (in Chinese)
76	田昊伦. PEDV流行株的分离鉴定及鹌鹑源卵黄抗体的研制[D]. 咸阳: 西北农林科技大学, 2021.
	TIAN H L. Isolation and identification of PEDV strains and development of quail-derived yolk antibodies[D]. Xianyang: Northwest A & F University, 2021. (in Chinese)

化学药物 Chemical drugs	分类 Classification	EC₅₀/(μmol·L^-1)	作用机制 Mechanism	参考文献 Reference
盐霉素 Salinomycin	抗生素	1.617	抑制PEDV的复制阶段；激活MAPK通路	[6-7]
两性霉素B Amphotericin B	抗生素	0.5/0.3	抑制PEDV入胞和细胞巨胞饮作用	[8]
松萝酸 Usnic acid	抗生素	-	抑制PEDV的复制阶段；抑制细胞的自噬过程	[9]
伊维菌素 Ivermectin	抗生素	7.05	抑制PEDV的释放阶段；诱导细胞周期阻滞	[10]
巴弗洛霉素A1 Bafilomycin A1	抗生素	-	抑制PEDV的复制	[11]
利福平 Rifampicin	抗生素	-	抑制PEDV的复制	[12]
瑞德西韦 Remdesivir	核苷类似物	11.97	抑制RdRp活性；最佳的给药方式为治疗性给药	[14-15]
莫诺拉韦 Molnupiravir	核苷类似物	12.30	抑制RdRp活性	[18]
烟酰胺 Nicotinamide	维生素类	-	通过激活ERK1/2/MAPK通路下调转录因子的表达	[19]
1, 25-二羟基维生素D₃ 1, 25-dihydroxyvitamin D₃	维生素类	-	通过ERK1/2信号通路；抑制NF-κB和JAK/STAT信号通路	[20-21]
金鸡宁 Cinchonine	抗疟药	-	通过诱导细胞自噬来抑制PEDV的复制	[22]
依福地平 Ifenprodil	二氢吡啶类	13/11	抑制PEDV的入胞阶段	[23]
氯化锂 Lithium chloride	抗糖尿病药	-	抑制PEDV诱导的细胞凋亡	[24]
氯硝柳胺 Niclosamide	抗蠕虫药	0.246	抑制PEDV的进入阶段	[25]

[1]	吴超, 明文含, 卢姝婉, 杨彩梅, 刘金松, 马翔, 张瑞强. 猪流行性腹泻病毒的天然免疫逃避机制及其防控研究进展[J]. 畜牧兽医学报, 2025, 56(6): 2590-2599.
[2]	周敏, 汤德元, 曾智勇, 王彬, 黄涛, 胡雯雯, 毛茵茗, 周飘, 何松. 猪流行性腹泻病毒蛋白与宿主蛋白相互作用的研究进展[J]. 畜牧兽医学报, 2025, 56(6): 2600-2612.
[3]	李程程, 赵永祥, 曹秋霞, 宋旭, 李宇鹏, 范宝超, 郭容利, 徐业芬, 李彬. 紧密连接蛋白CLDN4促进猪流行性腹泻病毒感染[J]. 畜牧兽医学报, 2025, 56(6): 2826-2835.
[4]	胡米, 沈瑶歆, 范宝超, 孙敏, 周金柱, 郭容利, 李彬. Eudragit L100修饰的铝锰双金属有机框架作为猪流行性腹泻灭活疫苗口服递送载体的初步评价[J]. 畜牧兽医学报, 2025, 56(5): 2292-2230.
[5]	邬沛伶, 李依璇, 王浩杰, 李亚菲, 刘绍蒙, 刘青芸, 王湘如. 猪流行性腹泻疫苗研究进展[J]. 畜牧兽医学报, 2025, 56(3): 1042-1058.
[6]	余昕雅, 何海健, 王磊, 倪语晨, 杜静, 周莹珊, 董婉玉, 王晓杜. LncRNA 18850对猪流行性腹泻病毒复制的影响[J]. 畜牧兽医学报, 2025, 56(3): 1366-1375.
[7]	张冬萱, 王智豪, 乔岩, 赵肖肖, 范松杰, 张超. 猪流行性腹泻病毒S1蛋白的原核表达及其核酸适配体的筛选[J]. 畜牧兽医学报, 2025, 56(2): 839-850.
[8]	刘维哲, 罗成刚, 袁蓉, 廖艺杰, 文艺悯, 孙莹, 俞恩波, 曹三杰, 黄小波. 一株猪流行性腹泻病毒强毒株的分离与鉴定[J]. 畜牧兽医学报, 2024, 55(7): 3049-3063.
[9]	李栋梁, 郑关民, 李帅, 朱洪森, 吴超. 猪流行性腹泻病毒感染仔猪空肠转录组差异表达分析[J]. 畜牧兽医学报, 2024, 55(6): 2652-2661.
[10]	徐红, 商红旗, 张雪, 钱嘉莉, 王传红, 宋旭, 宝梅英, 刘诗雨, 张格格, 郭容利, 赵永祥, 范宝超, 李彬. C8orf4基因编码蛋白对猪流行性腹泻病毒体外复制的抑制效应[J]. 畜牧兽医学报, 2024, 55(5): 2100-2108.
[11]	王静, 张淑娟, 胡霞, 刘向阳, 张兴翠, 宋振辉. CD44通过影响猪流行性腹泻病毒复制调节钠氢交换体3活性[J]. 畜牧兽医学报, 2024, 55(5): 2176-2185.
[12]	胡泽奇, 李润成, 谭祖明, 谢秀艳, 王江平, 秦乐娟, 李荣, 葛猛. PEDV、PoRVA和PDCoV TaqMan三重RT-qPCR检测方法的建立与初步应用[J]. 畜牧兽医学报, 2024, 55(5): 2267-2272.
[13]	林莉莉, 张梦迪, 朱琳琳, 马海龙, 孙琪, 何启盖, 张梦佳, 李文涛. 基于猪流行性腹泻病毒GⅡb亚型重组荧光病毒中和抗体检测方法的建立[J]. 畜牧兽医学报, 2024, 55(4): 1649-1660.
[14]	任莉鑫, 张静怡, 徐沙沙, 杨柳, 张兴翠, 宋振辉. ACE2对猪流行性腹泻病毒体外感染传代猪小肠上皮细胞的影响[J]. 畜牧兽医学报, 2024, 55(3): 1238-1248.
[15]	周建浩, 王东方, 刘影, 王淑娟, 马震原, 谢彩华, 赵雪丽, 杨海波, 冯桂丹, 康台生, 胡煜锋, 李博文, 闫若潜. 猪流行性腹泻病毒微滴式数字PCR定量检测方法的建立及初步应用[J]. 畜牧兽医学报, 2024, 55(1): 413-418.

体外对猪流行性腹泻病毒复制具有抑制效应的物质

Substances with Inhibitory Effects on Porcine Epidemic Diarrhea Virus Replication in vitro

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 76

相关文章 15

编辑推荐

Metrics

本文评价