甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用 机制研究：生物信息学分析

doi:10.19871/j.cnki.xfcrbzz.2025.03.007

新发传染病电子杂志 ›› 2025, Vol. 10 ›› Issue (3): 40-46.doi: 10.19871/j.cnki.xfcrbzz.2025.03.007

甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用机制研究：生物信息学分析

徐静¹, 陈尚², 王娴玮¹, 贾舒², 范绪涛³

1.济宁医学院附属医院感染性疾病科,山东济宁 272000;
2.济宁医学院附属医院医学研究中心,山东济宁 272000;
3.济宁医学院附属医院脊柱外科,山东济宁 272000

收稿日期:2024-11-12 出版日期:2025-06-30 发布日期:2025-07-24
通讯作者: 范绪涛,Email:xutaofan@mail.jnmc.edu.cn
基金资助:
山东省中医药科技面上项目（M-2023121）

Study on the mechanisms of glycyrrhizic acid and its derivatives targeting human parainfluenza virus and rubella virus: bioinformatics analysis

Xu Jing¹, Chen Shang², Wang Xianwei¹, Jia Shu², Fan Xutao³

1. Department of Infectious Diseases, The Affiliated Hospital of Jining Medical University, Shandong Jining 272000, China;
2. Medical Research Center, The Affiliated Hospital of Jining Medical University, Shandong Jining 272000, China;
3. Department of Spinal Surgery, The Affiliated Hospital of Jining Medical University, Shandong Jining 272000, China

Received:2024-11-12 Online:2025-06-30 Published:2025-07-24

摘要/Abstract

摘要： 目的本研究旨在探索甘草酸（glycyrrhizic acid,GL）及其衍生物甘草次酸（glycyrrhetinic acid,GA）、甘草酸铵（ammonium glycyrrhizinate,AG）、甘草酸钠（sodium glycyrrhizinate,SG）和甘草酸二钾（dipotassium glycyrrhizinate,DG）对人副流感病毒（human parainfluenza virus,HPIV）和风疹病毒（rubella virus,RuV）的潜在抗病毒机制,以期为开发新型抗病毒疗法提供理论依据。方法采用现代生物信息学方法,通过Super-PRED数据库预测GL及其衍生物的可能靶蛋白,进行基因本体论（gene ontology,GO）和京都基因与基因组百科全书 (Kyoto encyclopedia of genes and genomes,KEGG）功能富集分析,以揭示靶蛋白的生物过程和信号通路。通过蛋白质互作网络（protein-protein interaction,PPI）分析识别关键靶蛋白,并进行分子对接研究,评估GL及其衍生物与目标蛋白的结合亲和力。结果 GL及其衍生物与59个呼吸道病毒靶蛋白有潜在相互作用,其中信号转导与转录激活因子3（signal transducer and activator of transcription 3,STAT3）、Toll样受体4（toll-like receptor 4,TLR4）、补体C5a受体 1（complement C5a receptor 1,C5AR1）和核因子κB亚基1（nuclear factor kappa B subunit 1,NFKB1）在HPIV和RuV感染中起重要作用。这些靶蛋白在多条信号通路中表现出参与性,包括免疫调节和炎症反应。分子对接研究结果显示GL与C5AR1和STAT3、AG与C5AR1以及DG与STAT3表现出较高的结合亲和力。结论 GL及其衍生物通过多靶点机制展现出对HPIV和RuV的抗病毒活性。研究为GL应用于抗病毒治疗提供了理论支持,并指出其作为潜在多靶点治疗药物的开发价值。

关键词: 甘草酸, 衍生物, 人副流感病毒, 风疹病毒, 蛋白质互作网络, 分子对接, 生物信息学

Abstract: Objective This study aimed to explore the potential antiviral mechanisms of glycyrrhizic acid (GL) and its derivatives, including glycyrrhetinic acid (GA), ammonium glycyrrhizinate (AG), sodium glycyrrhizinate (SG), and dipotassium glycyrrhizinate (DG), against human parainfluenza virus (HPIV) and rubella virus (RuV) to provide a theoretical basis for the development of novel antiviral therapies. Method Modern bioinformatics methods were used. First, the possible target proteins of GL and its derivatives were predicted through the Super-PRED database. Next, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses were performed to reveal the biological processes and signaling pathways of the target proteins. Key target proteins were identified through protein-protein interaction (PPI) analysis, and molecular docking studies were conducted to evaluate the binding affinity of GL and its derivatives to target proteins.Result The analysis showed that GL and its derivatives were predicted to have potential interactions with 59 respiratory virus target proteins. Among them, signal transducer and activator of transcription 3 (STAT3), Toll-like receptor 4 (TLR4), complement C5a receptor 1 (C5AR1), and nuclear factor kappa B subunit 1 (NFKB1) played important roles in HPIV and RuV infections. These target proteins showed participation in multiple signaling pathways, including immune regulation and inflammatory responses. Molecular docking showed that GL bound to C5AR1 and STAT3, AG bound to C5AR1, and DG bound to STAT3 with high binding affinity. Conclusion GL and its derivatives exhibit antiviral activity against HPIV and RuV through a multi-target mechanism. This study provides theoretical support for the application of GL in antiviral therapy and indicates its potential value as a multi-target therapeutic agent.

Key words: Glycyrrhizic acid, Derivative, Human parainfluenza virus, Rubella virus, Protein-Protein Interaction, Molecular docking, Bioinformatics

中图分类号:

R373.1

徐静, 陈尚, 王娴玮, 贾舒, 范绪涛. 甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用机制研究：生物信息学分析[J]. 新发传染病电子杂志, 2025, 10(3): 40-46.

Xu Jing, Chen Shang, Wang Xianwei, Jia Shu, Fan Xutao. Study on the mechanisms of glycyrrhizic acid and its derivatives targeting human parainfluenza virus and rubella virus: bioinformatics analysis[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(3): 40-46.

参考文献

[1] LEUNG NHL.Transmissibility and transmission of respiratory viruses[J]. Nat Rev Microbiol, 2021, 19(8): 528-545.
[2] BRANCHE AR, FALSEY AR.Parainfluenza Virus Infection[J]. Semin Respir Crit Care Med, 2016, 37(4):538-554.
[3] XU J, KONG J, LYU B, et al.The Capsid Protein of Rubella Virus Antagonizes RNA Interference in Mammalian Cells[J]. Viruses, 2021, 13(2):154.
[4] PAWE CZYK M, KOWALSKI ML.The Role of Human Parainfluenza Virus Infections in the Immunopathology of the Respiratory Tract[J]. Curr Allergy Asthma Rep, 2017, 17(3):16.
[5] DAS PK, KIELIAN M.Rubella virus assembly requirements and evolutionary relationships with novel rubiviruses[J]. mBio, 2024, 15(10):e0196524.
[6] HOUR MJ, CHEN Y, LIN CS, et al.Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity[J]. Int J Mol Sci, 2022, 23(18):10309.
[7] WANG L, YANG R, YUAN B, et al.The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb[J]. Acta Pharm Sin B, 2015, 5(4):310-315.
[8] FIORE C, EISENHUT M, KRAUSSE R, et al.Bielenberg J. Antiviral effects of Glycyrrhiza species[J]. Phytother Res, 2008, 22(2):141-148.
[9] SAKAI-SUGINO K, UEMATSU J, KAMADA M, et al.Glycyrrhizin inhibits human parainfluenza virus type 2 replication by the inhibition of genome RNA, mRNA and protein syntheses[J]. Drug Discov Ther, 2017, 11(5):246-252.
[10] DAS PK, GONZALEZ PA, JANGRA RK, et al.A single-point mutation in the rubella virus E1 glycoprotein promotes rescue of recombinant vesicular stomatitis virus[J]. mBio, 2024, 15(3):e0237323.
[11] LIU Y, XU Q, DENG F, et al.HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway[J]. J Exp Clin Cancer Res, 2023, 42(1):38.
[12] FENG Y, CHEN Y, WU X, et al.Interplay of energy metabolism and autophagy[J]. Autophagy, 2024, 20(1):4-14.
[13] TAN D, TSENG HHL, ZHONG Z, et al.Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications[J]. Int J Mol Sci, 2022, 23(19):10988.
[14] CHENG X, LIU Y, QI B, et al.Glycyrrhizic acid alleviated MI/R-induced injuries by inhibiting Hippo/YAP signaling pathwaysl[J]. Cell Signa, 2024, 115:111036.
[15] SUN ZG, ZHAO TT, LU N, et al.Research Progress of Glycyrrhizic Acid on Antiviral Activity[J]. Mini Rev Med Chem, 2019, 19(10):826-832.
[16] WANG Y, LIU W, XU Y, et al.Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins[J]. Nat Chem Biol, 2023, 19(11):1351-1360.
[17] HU X, FENG J, ZHOU Q, et al.Respiratory Syncytial Virus Exacerbates Kidney Damages in IgA Nephropathy Mice via the C5a-C5aR1 Axis Orchestrating Th17 Cell Responses[J]. Front Cell Infect Microbiol, 2019, 9:151.
[18] SILVA BM, GOMES GF, VERAS FP, et al.C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps[J]. J Clin Invest, 2023, 133(12):e163105.
[19] ISHIDA T, TAKAGI K, WANG G, et al.A Greater Increase in Complement C5a Receptor 1 Level at Onset and a Smaller Decrease in Immunoglobulin G Level after Recovery in Severer Coronavirus Disease 2019 Patients: A New Analysis of Existing Data with a New Two-Tailed t-Test[J]. Biology (Basel), 2023, 12(9):1176.
[20] QIN S, YAO X, LI W, et al.Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients[J]. Cell Death Dis, 2023, 14(4):286.
[21] RABY AC, HOLST B, DAVIES J, et al.TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2[J]. Eur J Immunol, 2011, 41(9):2741-2752.
[22] ZAAL A, NOTA B, MOORE KS, et al.TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3Kβ, SGK1, and FOXO transcription factors[J]. J Leukoc Biol, 2017, 102(4):1035-1054.
[23] ZHAO C, WANG W, BAI Y, et al. Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells[J]. bioRxiv [Preprint].2023, 2023.09.20.558606.
[24] PINKHAM C, AN S, LUNDBERG L, et al.The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection[J]. Virology, 2016, 496:175-185.
[25] LIU S, LIU S, YU Z, et al.STAT3 regulates antiviral immunity by suppressing excessive interferon signaling[J]. Cell Rep, 2023, 42(7):112806.
[26] XU Y, QI W, WANG X, et al.Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences[J]. J Viral Hepat, 2022, 29(7):569-578.

甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用机制研究：生物信息学分析

Study on the mechanisms of glycyrrhizic acid and its derivatives targeting human parainfluenza virus and rubella virus: bioinformatics analysis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics

本文评价

甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用 机制研究：生物信息学分析

Study on the mechanisms of glycyrrhizic acid and its derivatives targeting human parainfluenza virus and rubella virus: bioinformatics analysis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics

本文评价

甘草酸及其衍生物靶向人副流感病毒与风疹病毒的作用机制研究：生物信息学分析