天然产物抗猪流行性腹泻病毒研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-0372

摘要/Abstract

摘要：

猪流行性腹泻病毒（porcine epidemic diarrhea virus，PEDV）是一种引起仔猪呕吐、急性腹泻和脱水等症状的冠状病毒，仔猪的死亡率高达100%，给全球养猪业造成巨大经济损失。疫苗接种是防控猪流行性腹泻的关键途径，然而对于不断出现的PEDV变异毒株，现有的疫苗已不能提供充足的保护。天然产物具有来源广、作用多样、副作用低以及不易产生耐药性等优势，且已有许多研究证实多种天然产物具有抗PEDV的活性，具有广阔的应用前景。本文就中草药单体、单味中药提取物、中药复方制剂、微生物代谢物、藻类和动物来源的天然产物在抗PEDV的研究现状进行概述，以期为抗PEDV药物的创制提供借鉴及参考。

关键词: 猪流行性腹泻病毒, 中草药单体物质, 中草药提取物, 天然产物, 抗病毒

Abstract:

Porcine epidemic diarrhea virus（PEDV）causes a coronavirus disease characterized by vomiting，acute diarrhea，dehydration，and up to 100% mortality in piglets，leading to huge economic losses in the global swine industry. Vaccination remains the most effective way to prevent and control PED. However，the existing vaccines no longer provide sufficient protective immunity against the new emerging PEDV variants. Natural compounds have the advantages of wide sources，diverse effects，low side effects and little drug-resistance，and were proved to have the activities against PEDV，showing a broad application prospect. Hereby we gather and discuss the current information about the anti-PEDV activities of natural compounds including plant-derived products，single medicinal herb extracts，Chinese herbal compound preparation，microbial metabolites，compounds derived from algae and animals，aiming to provide insights and references for the development of potential anti-PEDV drugs.

Key words: porcine epidemic diarrhea virus, plant-derived products, medicinal herb extracts, natural compounds, antiviral

成温玉, 张博昕, 赵鸿远, 陈艳, 谢娟平. 天然产物抗猪流行性腹泻病毒研究进展[J]. 生物技术通报, 2022, 38(12): 127-136.

CHENG Wen-yu, ZHANG Bo-xin, ZHAO Hong-yuan, CHEN Yan, XIE Juan-ping. Research Progress in Natural Products Against Porcine Epidemic Diarrhea Virus[J]. Biotechnology Bulletin, 2022, 38(12): 127-136.

图/表 2

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化合物/成分 Compound/Component	来源 Source	分类 Classification	EC₅₀/IC₅₀	作用机制 Mechanism of action	参考文献 Reference
银杏多糖	银杏外果皮	植物多糖	（1.7±1.3）g/mL	阻碍PEDV对细胞的吸附和侵入	[6]
马齿苋多糖	马齿苋	植物多糖		阻碍PEDV对细胞的吸附并能抑制病毒感染引起的炎症细胞因子分泌	[7]
黄芪多糖	发酵黄芪	植物多糖		抑制PEDV的复制；增强机体免疫反应	[8]
PCP1.1，1.2，2.1和2.2	广藿香	植物多糖		抑制PEDV增殖；阻断病毒侵入细胞	[9]
AOFP3	益智仁	植物多糖		增强宿主细胞抗氧化活性，降低PEDV感染诱导的ROS	[10]
槲皮素	中草药	黄酮类	2.12-2.56 μmol/L	与PEDV 3CLpro结合并抑制蛋白酶活性	[13]
槲皮素-7-鼠李糖苷	中草药	黄酮类	0.014 μg/mL	影响PEDV感染的初始阶段	[14-15]
黄腐酚	啤酒花	类黄酮	3.865 μmol/L	降低PEDV感染诱导的ROS	[16-17]
表没食子儿茶素没食子酸酯	茶叶	多酚	12.39 μmol/L	阻碍PEDV的附着、入侵、复制和组装	[19-20]
金丝桃素	贯叶连翘	二蒽酮	（3.53±0.33）μmol/L	与PEDV 3CLpro结合并抑制蛋白酶的活性	[21]
黄连素	黄连、黄柏	生物碱		抑制PEDV的复制和组装，减弱病毒诱导的细胞凋亡反应	[22]
番茄碱	番茄	生物碱	3.447 μmol/L	与PEDV 3CLpro结合并抑制蛋白酶的活性	[18]
高三尖杉酯碱	三尖杉属植物	生物碱	0.112 μmol/L	抑制PEDV增殖	[23]
甘草酸	甘草	三萜类皂苷		阻碍病毒侵入和复制；减轻病毒感染引起的细胞炎症反应	[24-25]
七叶皂苷	七叶树种子	皂苷类		抑制PEDV的复制	[26]
欧当归内酯A	川芎	苯酞类		调控ROS介导的内质网应激反应；抑制PEDV对细胞的吸附或侵入	[27]
Oleanane triterpene 6，9，11，13	山茶花	五环三萜类	0.28-0.93 μmol/L	抑制PEDV蛋白的合成	[28]
Coumarin compound 5	防风	香豆素类	（4.85±0.43）μmol/L	抑制PEDV核衣壳蛋白和棘突蛋白的合成	[29]
Phenolic compound 15，16	柠檬清风藤	酚类	7.5-8.0 μmol/L	抑制PEDV的复制	[30]
芦荟提取物	芦荟			直接杀灭病毒粒子；抑制PEDV复制	[31]
淫羊藿水浸提物	淫羊藿			增强机体免疫反应；抑制PEDV增殖	[32]
金银花水浸提物	金银花			抑制PEDV增殖；调节机体免疫反应	[32]
辣木叶水浸提物	辣木			抑制PEDV诱导的细胞凋亡；降低PEDV诱导的炎症反应	[34]
闭脉斑果藤乙醇浸提物	闭脉斑果藤		0.15 μg/mL	抑制PEDV增殖	[35]
Griffithsin	海洋红藻	蛋白		阻碍PEDV的附着；干扰PEDV在细胞间的传播	[44]
Phlorotannin compound 4，5	褐藻苷苔	多酚类	12.2-14.6 μmol/L	抑制PEDV RNA和蛋白的合成；通过血凝抑制反应阻碍病毒的侵入	[45]
Surfactin	枯草芽孢杆菌	脂肽		直接插入到PEDV囊膜中，阻碍病毒囊膜与宿主细胞膜融合	[47]
Xiamycin D	链霉菌	吲哚倍半萜	0.93 μmol/L	抑制PEDV结构蛋白的表达	[48]
盐霉素	白色链霉菌	羧酸聚醚类		调控ERK1/2和p38MAPK通路发挥抗病毒反应	[49]
麦角甾醇过氧化物	真菌、地衣、海绵	甾醇		直接杀灭病毒粒子；通过抑制p53蛋白的激活和ROS生成降低PEDV感染诱导的细胞凋亡反应	[50]
月桂酸甘油酯	母乳	脂肪酸		调控机体免疫应答并维持体内稳态发挥抗PEDV功能	[12]
褪黑素	动物松果腺	吲哚类		抑制PEDV的侵入和复制	[51]
壳聚糖	甲壳类动物	多糖		直接杀灭病毒粒子	[52]

化合物/成分 Compound/Component	来源 Source	分类 Classification	EC₅₀/IC₅₀	作用机制 Mechanism of action	参考文献 Reference
银杏多糖	银杏外果皮	植物多糖	（1.7±1.3）g/mL	阻碍PEDV对细胞的吸附和侵入	[6]
马齿苋多糖	马齿苋	植物多糖		阻碍PEDV对细胞的吸附并能抑制病毒感染引起的炎症细胞因子分泌	[7]
黄芪多糖	发酵黄芪	植物多糖		抑制PEDV的复制；增强机体免疫反应	[8]
PCP1.1，1.2，2.1和2.2	广藿香	植物多糖		抑制PEDV增殖；阻断病毒侵入细胞	[9]
AOFP3	益智仁	植物多糖		增强宿主细胞抗氧化活性，降低PEDV感染诱导的ROS	[10]
槲皮素	中草药	黄酮类	2.12-2.56 μmol/L	与PEDV 3CLpro结合并抑制蛋白酶活性	[13]
槲皮素-7-鼠李糖苷	中草药	黄酮类	0.014 μg/mL	影响PEDV感染的初始阶段	[14-15]
黄腐酚	啤酒花	类黄酮	3.865 μmol/L	降低PEDV感染诱导的ROS	[16-17]
表没食子儿茶素没食子酸酯	茶叶	多酚	12.39 μmol/L	阻碍PEDV的附着、入侵、复制和组装	[19-20]
金丝桃素	贯叶连翘	二蒽酮	（3.53±0.33）μmol/L	与PEDV 3CLpro结合并抑制蛋白酶的活性	[21]
黄连素	黄连、黄柏	生物碱		抑制PEDV的复制和组装，减弱病毒诱导的细胞凋亡反应	[22]
番茄碱	番茄	生物碱	3.447 μmol/L	与PEDV 3CLpro结合并抑制蛋白酶的活性	[18]
高三尖杉酯碱	三尖杉属植物	生物碱	0.112 μmol/L	抑制PEDV增殖	[23]
甘草酸	甘草	三萜类皂苷		阻碍病毒侵入和复制；减轻病毒感染引起的细胞炎症反应	[24-25]
七叶皂苷	七叶树种子	皂苷类		抑制PEDV的复制	[26]
欧当归内酯A	川芎	苯酞类		调控ROS介导的内质网应激反应；抑制PEDV对细胞的吸附或侵入	[27]
Oleanane triterpene 6，9，11，13	山茶花	五环三萜类	0.28-0.93 μmol/L	抑制PEDV蛋白的合成	[28]
Coumarin compound 5	防风	香豆素类	（4.85±0.43）μmol/L	抑制PEDV核衣壳蛋白和棘突蛋白的合成	[29]
Phenolic compound 15，16	柠檬清风藤	酚类	7.5-8.0 μmol/L	抑制PEDV的复制	[30]
芦荟提取物	芦荟			直接杀灭病毒粒子；抑制PEDV复制	[31]
淫羊藿水浸提物	淫羊藿			增强机体免疫反应；抑制PEDV增殖	[32]
金银花水浸提物	金银花			抑制PEDV增殖；调节机体免疫反应	[32]
辣木叶水浸提物	辣木			抑制PEDV诱导的细胞凋亡；降低PEDV诱导的炎症反应	[34]
闭脉斑果藤乙醇浸提物	闭脉斑果藤		0.15 μg/mL	抑制PEDV增殖	[35]
Griffithsin	海洋红藻	蛋白		阻碍PEDV的附着；干扰PEDV在细胞间的传播	[44]
Phlorotannin compound 4，5	褐藻苷苔	多酚类	12.2-14.6 μmol/L	抑制PEDV RNA和蛋白的合成；通过血凝抑制反应阻碍病毒的侵入	[45]
Surfactin	枯草芽孢杆菌	脂肽		直接插入到PEDV囊膜中，阻碍病毒囊膜与宿主细胞膜融合	[47]
Xiamycin D	链霉菌	吲哚倍半萜	0.93 μmol/L	抑制PEDV结构蛋白的表达	[48]
盐霉素	白色链霉菌	羧酸聚醚类		调控ERK1/2和p38MAPK通路发挥抗病毒反应	[49]
麦角甾醇过氧化物	真菌、地衣、海绵	甾醇		直接杀灭病毒粒子；通过抑制p53蛋白的激活和ROS生成降低PEDV感染诱导的细胞凋亡反应	[50]
月桂酸甘油酯	母乳	脂肪酸		调控机体免疫应答并维持体内稳态发挥抗PEDV功能	[12]
褪黑素	动物松果腺	吲哚类		抑制PEDV的侵入和复制	[51]
壳聚糖	甲壳类动物	多糖		直接杀灭病毒粒子	[52]