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

Abstract

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

CLC Number:

S853.74

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.

References

[1] YAN S, LIU X, ZHANG G, et al. Analysis of antigenicity and pathogenicity reveals major differences among QX-like infectious bronchitis viruses and other serotypes[J]. Vet Microbiol, 2017, 203:167-173.
[2] El-TWAB A A, SHARAWI S, NASEF S, et al. Natural co-infection of Escherichia coli and infectious bronchitis virus in broilers and layers flocks[J]. Benha Veterinary Medical Journal, 2018, 34(2):213-220.
[3] SID H, BENACHOUR K, RAUTENSCHLEIN S. Co-infection with multiple respiratory pathogens contributes to increased mortality rates in algerian poultry flocks[J]. Avian Dis, 2015, 59(3):440-446.
[4] 李定刚. 禽用纯中药免疫增强剂(玉屏风口服液)的研制[Z]. 河北省,保定冀中药业有限公司,2010-08-13.
LI D G. Development of pure traditional Chinese medicine immune enhancer for poultry (Yupingfeng oral liquid) [Z]. Hebei Province, Baoding Jizhong Pharmaceutical Co., Ltd., 8-13, 2010. (in Chinese)
[5] 温馨，江耀伦，武力.双黄连药理作用及其在家禽疫病防控的应用[J]. 养禽与禽病防治, 2017(6):7-9.
WEN X, JIANG Y L, WU L. Pharmacological effects of Shuanghuanglian and its application in poultry disease prevention and control [J]. Poultry Breeding and Disease Prevention and Control, 2017(6): 7-9. (in Chinese)
[6] 雷亚萍, 周世伟, 滕雨萌, 等. 麻杏石甘口服液治疗肉鸡感染鸡毒支原体的效果评价[J]. 畜牧兽医学报, 2023, 54 (12): 5264-5274.
LEI Y P, ZHOU S W, TENG Y M, et al. Evaluation of the efficacy of Maxing Shigan oral solution in treating chicken infection with Mycoplasma gallisepticum in broiler chickens [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54 (12): 5264-5274. (in Chinese)
[7] 冯海鹏，李建喜，王学智，等.中兽药复方组合与抗生素防治肉鸡呼吸道疾病的协同效应[J].中国畜牧兽医, 2020, 47(3): 940-947.
FENG H P, LI J X, WANG X Z, et al. The synergistic effect of traditional Chinese veterinary medicine compound combination and antibiotic prevention and treatment of respiratory diseases in broiler chickens [J]. Chinese Journal of Animal Husbandry & Veterinary Medicine, 2020, 47 (3): 940-947. (in Chinese)
[8] KUN Y H, SAMIK G, HIROAKI K, et al. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J]. PLoS One, 2013, 8(12):e83922.
[9] XI L, LE P L, XIN Y X, et al. A network pharmacology study on the effects of Ma Xing Shi Gan decoction on Influenza science direct[J]. Digital Chinese Medicine, 2020, 3(3):163-179.
[10] 黄浪，刘言薇，刘中勇，等.基于网络药理学和分子对接技术的玉屏风散防治新型冠状病毒肺炎活性化合物研究[J]. 中药药理与临床, 2020, 36(2): 116-121.
HUANG L, LIU Y W, LIU Z Y, et al. Research on the active compounds of Yupingfeng Powder in preventing and treating novel coronavirus pneumonia based on network pharmacology and molecular docking technology [J]. Pharmacology and Clinics of Chinese Materia Medica, 2020, 36 (2): 116-121. (in Chinese)
[11] 郝江花，孙娜，孙盼盼，等. 基于网络药理学和分子对接分析苦参碱抗PRRSV的作用机制[J]. 畜牧兽医学报, 2021, 52 (3): 809-819.
HAO J H, SUN N, SUN P P, et al. Analysis of the mechanism of action of matrine against PRRSV based on network pharmacology and molecular docking [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52 (3): 809-819. (in Chinese)
[12] 吴娜，饶智颖，李华山，等.基于网络药理学和分子对接的理肠四方治疗溃疡性结肠炎分子机制的比较研究[J].中药材, 2020, 43(1): 186-192.
WU N, RAO Z Y, LI H S, et al. Comparative study on the molecular mechanisms of Lichang Sifang in treating ulcerative colitis based on network pharmacology and molecular docking [J]. Chinese Herbal Medicine, 2020, 43 (1): 186-192. (in Chinese)
[13] WEISS S R, NAVAS M S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus [J]. Microbiol Mol Biol Rev, 2006, 69(4): 635-664.
[14] CAVANAGH D. Coronavirus avian infectious bronchitis virus[J]. Vet Res, 2007, 38(2): 281-297.
[15] PROMKUNTOD N, VAN E R E W, DE V G, et al. Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus[J]. Virology, 2014, 448: 26-32.
[16] SHANG J, ZHENG Y, YANG Y, et al. Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins[J]. PLoS Pathog, 2018, 14(4): e1007009.
[17] HU T T，CHENG C, LI H Y, et al. Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9[J]. Protein Sci, 2017, 26(5): 1037-1048.
[18] XUE X Y, YU H W, YANG H T, et al. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design[J]. J Virol, 2008, 82(5): 2515-27.
[19] WU W, LI R, LI X, et al. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry[J]. Viruses, 2015, 8(1): 6.
[20] ZHANG R, AI X, DUAN Y, et al. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways[J]. Biomed Pharmacother, 2017, 89: 660-672.
[21] RUANSIT W, CHARERNTANTTANAKUL W. Oral supplementation of quercetin in PRRSV-1 modified-live virus vaccinated pigs in response to HP-PRRSV-2 challenge[J]. Vaccine, 2020, 38(19): 3570-3581.
[22] CHENG P, WANG T, LI W, et al. Baicalin alleviates Lipopolysaccharide-induced liver inflammation in chicken by suppressing TLR4-mediated NF-κB pathway[J]. Front Pharmacol, 2017, 8:547.
[23] HU N, WANG C, DAI X, et al. Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-κB signaling pathway[J]. J Ethnopharmacol, 2020, 248: 112361.
[24] SHIN E M, ZHOU H Y, GUO L Y, et al. Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS-stimulated RAW264.7 macrophages[J].Int Immunopharmacol, 2008, 8(11): 1524-1532.
[25] MEN X Y, LI S, CAI X J, et al. Antiviral activity of luteolin against pseudorabies virus in vitro and in vivo [J]. Animals (Basel), 2023, 13(4): 761.
[26] WANG J R, ZENG X Y, GOU J 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.
[27] THEERAWATANASIRIKUL S, THANGTHAMNIYOM N, KUO C J, et al. Natural phytochemicals, luteolin and isoginkgetin, inhibit 3C protease and infection of FMDV, in silico and in vitro[J]. Viruses, 2021, 13(11): 2118.
[28] CHEN Y, GUO Y, SONG Z, et al. Luteolin restricts ASFV replication by regulating the NF-kappaB/STAT3/ ATF6 signaling pathway[J]. Vet Microbio, 2022, 273: 109527.

The Potential Drugs Screening against IBV Infection based on Network Pharmacology and Molecular Docking and Validation in vitro

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	ZHAO Yujie, WAN Baoxia, WANG Jiaqi, SUN Siyu, LENG Xinyang, CUI Yizhe. Mechanism of Action of Dandelion Addition to Ration to Enhance the Immune Performance of Geese Based on Network Pharmacological Analysis [J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(9): 4698-4707.
[2]	LI Xiaodie, PAN Shiqin, WANG Lu, CHENG Zhentao, OU Deyuan, SONG Xuqin, YANG Jian. Research Progress on the Anti-inflammatory Mechanism of Traditional Chinese Veterinary Medicine based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(8): 3701-3721.
[3]	CHEN Zehan, ZHANG Ruoyi, LIN Huiying, ZENG Chunli, LIN Fu, LI Jian. Anti-inflammatory Effects of Chelidonium majus on IPEC-J2 Cells based on HPLC Fingerprint and Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(5): 2466-2480.
[4]	ZHANG Beiwen, LI Hongxi, WENG Chengzhen, HUANG Xinxin, LI Xiaobing, QIU Longxin, CHEN Hongbo. The Mechanism of Bidens pilosa L. in the Treatment of Bacterial Diarrhea in Poultry based on Network Pharmacological Analysis and Experimental Verification [J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(11): 5683-5696.
[5]	Anlin WEN, Yunyun YANG, Yongrong LUO, Ying YANG, Zhentao CHENG, Deyuan OU, Ming WEN. Network Pharmacologic Analysis and Experimential Verification on the Mechanism of Coptidis Rhizoma in Preventing Duck Viral Enteritis [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(7): 3225-3233.
[6]	XU Junjie, ZHANG Lutong, WANG Jinjie, CHEN Xiaochen, HE Weixian, CAI Chuanjiang, CHU Guiyan, YANG Gongshe. Exploring the Effect of Epimedium on Estrus of Gilts Based on Multiomics and Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1615-1628.
[7]	LIU Yuanhong, HU Yuhuan, ZHANG Li, YANG Pingrui, HU Weidong, MA Qi, BI Shicheng. Network Pharmacologic Analysis and Experimental Verification of Atractylodes Macrocephala-Cistanche Deserticola in the Treatment of Constipation [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(2): 834-845.
[8]	GONG Zhiguo, ZHAO Jiamin, GU Baichen, REN Peipei, YU Zhuoya, BAI Yunjie, LIU Xinyu, WANG Chao, LIU Bo. Exploring the Mechanism of Codonopsis pilosula in Alleviation of Acute Lung Injury in Escherichia coli Infected Mice Based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3571-3581.
[9]	ZHANG Xumei, WEI Yurong, XU Chenghui, YANG Tong, SHI Huijun, FU Qiang, YANG Li. To Analyze the Mechanism of Berberine in the Treatment of Salmonella Gallinarum Infection Based on Network Pharmacology and Experimental Verification [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3557-3570.
[10]	YANG Zihui, DONG Zhen, WU Huilan, TAN Bin, ZENG Jianguo. Analysis of the Material Basis and Mechanism of Action of Antioxidant Function of Taraxacum mongolicum based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(5): 2170-2185.
[11]	PAN Chanyuan, ZHAO Zixuan, DUAN Mingjie, JIANG Linshu, TONG Jinjin. The Mechanism of Artemisia carvifolia Alleviating Dairy Cow Oxidative Stress Predicted by Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1071-1084.
[12]	GONG Haoyang, WU Jiaxin, YANG Xiaoyu, XIE Weichun, WANG Xueying, LI Jiaxuan, JIANG Yanping, CUI Wen, LI Yijing, TANG Lijie. Research Progress in Antiviral Mechanism of Intestinal Microflora [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(12): 4910-4919.
[13]	CUI Enhui, XUE Yuhuan, LI Cixia, WANG Shuai, ZHU Xiaoyan, CHAI Xuejun, ZHAO Shanting. Network Pharmacological Analysis and Experimental Verification of Immunomodulatory Mechanisms of Eucommia ulmoides Leaf [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 403-413.
[14]	TIAN Wei, LI Xiumei, YANG Juan, WANG Xiaoying, ZHOU Weiwei, LI Zhongyuan, DAI Xiaofeng. Network Pharmacology Study on the Antibacterial Activity Components and Mechanism of Isatis indigotica [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(8): 2782-2793.
[15]	LIU Weiwei, ZHANG Yuxin, LI Xiumei, WANG Xiumin, ZHOU Weiwei, DAI Xiaofeng. Mechanism of Mori Folium in Improving Antioxidative Function of Chicken Based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(6): 1958-1970.