基于网络药理学和分子对接预测抗IBV感染的潜在药物及体外验证

doi:10.11843/j.issn.0366-6964.2025.12.041

摘要/Abstract

摘要：

旨在利用网络药理学探讨玉屏风口服液、麻杏石甘口服液和双黄连口服液联合应用防治禽呼吸道疾病的作用机制，通过分子对接技术筛选潜在抗IBV感染的活性成分，并验证木犀草素的抗病毒活性。在TCMSP和Uniprot数据库检索3种中药复方的入血成分和潜在作用靶点。在DrugBank, GeneCards, OMIM和PharmGkb数据库搜索疾病(呼吸道感染)的相关靶点。利用DAVID数据库对核心靶点进行GO富集和KEGG通路注释分析。利用PDBQT和AutoDock vina软件将主要活性成分与IBV-nsp9、S1及主要蛋白酶(M^pro)进行对接，细胞试验验证木犀草素的抗IBV活性。结果发现，三种中药复方中的活性成分黄芩素、连翘脂素、木犀草素、刺芒柄花素、山奈酚和槲皮素等活性成分可能通过FN1、IL-6、PTGS2等关键靶点发挥治疗禽呼吸道感染的作用。分子对接结果显示连翘脂素、山奈酚、甘草酸、木犀草素、槲皮素和异牡荆素均与IBV-nsp9、S1及M^pro具有较高的结合活性，通过细胞试验证实木犀草素能够抑制IBV在细胞中的复制和病毒空斑形成数量。本研究初步揭示了3种中药复方联合治疗禽呼吸道感染的基本药理作用机制，证实了木犀草素的体外抗IBV活性。

关键词: 网络药理学, 分子对接, 禽呼吸道感染, 抗病毒, 木犀草素

Abstract:

The aim of this study is exploring the mechanism of Yupingfeng oral liquid combined Maxingshigan oral liquid and Shuanghuanglian oral liquid to treat avian respiratory tract infection via network pharmacology, and screen potential anti-IBV drugs by molecular docking technique, as well verifying the anti-IBV activity of Luteolin. The blood entry components and potential targets in three traditional Chinese medicine compounds were retrieved in TCMSP and Uniprot database. The related targets of diseases (respiratory tract infection) were discovered in DrugBank, GeneCards, OMIM and PharmGkb databases, the DAVID database was used to analyze the GO enrichment and KEGG pathway annotation. Then, the key compounds were docked with IBV-nsp9, S1 and main proteases (M^pro) by PDBQT and AutoDock vina software. The anti-IBV activity of Luteolin was validated in Vero cell. The result exhibited that Baicalein, Phillygenin, Luteolin, Formononetin, Kaempferol and Quercetin in three traditional Chinese medicine prescriptions might play a role in the treatment of avian respiratory tract infection through key targets such as FN1, IL6 and PTGS2. Molecular docking result indicated that Phillygenin, Kaempferol, Glycyrrhizin, Luteolin, Quercetin and Isovitexin showed the strongest binding ability with IBV-nsp9, S1 and M^pro. The effect of Luteolin inhibiting IBV replication and the number of viral plaques were verified in Vero cell. The study preliminarily revealed the basic pharmacological effects mechanism of three kinds of traditional Chinese medicine combinations in the treatment of avian respiratory tract infection, and confirmed the anti-IBV effect of Luteolin in vitro.

Key words: network pharmacology, molecular docking, avian respiratory tract infection, antivirus, Letuolin

中图分类号:

S853.74

冯海鹏, 张康, 张景艳, 路晓荣, 李建喜. 基于网络药理学和分子对接预测抗IBV感染的潜在药物及体外验证[J]. 畜牧兽医学报, 2025, 56(12): 6397-6410.

FENG Haipeng, ZHANG Kang, ZHANG Jingyan, LU Xiaorong, LI Jianxi. The Potential Drugs Screening against IBV Infection based on Network Pharmacology and Molecular Docking and Validation in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(12): 6397-6410.

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中药复方 TCM	药物配伍 Drug compatibility	活性成分 Active ingredient	与疾病相关的靶基因 Diseases-related gene
玉屏风口服液 Yupingfeng Oral liquid	白术	7	49
	防风	18
	黄芪	20
双黄连口服液 Shuanghuanglian Oral liquid	黄芩	36	51
	金银花	23
	连翘	23
麻杏石甘口服液 Maxingshigan Oral liquid	甘草	92	21
	苦杏仁	19
	麻黄	23

靶点 Target	中药活性成分 Ingredient of TCM
FN1	汉黄芩素
IL6	木犀草素、槲皮素、汉黄芩素、千层纸素A、青藤碱、苦参碱
PTGS2	木犀草素、柚皮素、黄芩苷、黄芩新素、金圣草(黄)素、连翘脂素、牛蒡子苷、蝙蝠葛新、青藤碱、甘草酚、高车前素、金合欢素、雌酚酮、儿茶素
EGFR	木犀草素、槲皮素
JUN	木犀草素、槲皮素、汉黄芩素、β-胡萝卜素、β-谷甾醇、山奈酚、刺芒柄花素
STAT3	甘草查而酮A
VEGFA	木犀草素、槲皮素、黄芩素、β-胡萝卜素

化合物 Compound	化学式 Chemical formula	CAS号 No. of CAS	与IBV-nsp9结合能 Binding energy with IBV-nsp9	与IBV-S1结合能 Binding energy with IBV-S1	与IBV- M^pro结合能 Binding energy with IBV-M^pro
连翘脂素 Phillygenin	C₂₁H₂₄O₆	487-39-8	-29.3	-38.5	-37.6
甘草酚 Glycyrrhizin	C₂₁H₁₈O₆	23013-84-5	-29.7	-38.1	-35.9
木犀草素 Luteolin	C₁₅H₁₀O₆	491-70-3	-28.9	-38.1	-35.1
山奈酚 Kaempferol	C₁₅H₁₀O₆	520-18-3	-27.6	-35.1	-34.7
槲皮素 Quercetin	C₁₅H₁₀O⁷	117-39-5	-27.6	-35.6	-35.1
异牡荆素 Isovitexin	C₂₁H₂₀O₁₀	29702-25-8	-29.7	-37.2	-37.6

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