基于靶点和活性成分的筛选探讨连翘抗病毒作用机制

doi:10.5246/jcps.2024.06.040

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (6): 543-558.DOI: 10.5246/jcps.2024.06.040

基于靶点和活性成分的筛选探讨连翘抗病毒作用机制

孙娜^*(), 马烁, 靳琳萱, 张新, 周苗, 杨欢欢, 李文倩, 吴欣茹, 侯艳艳, 袁宇涵, 张玉, 舒朋华^*()

许昌学院食品与药学院, 河南许昌 461000

收稿日期:2023-11-13 修回日期:2024-01-12 接受日期:2024-03-05 出版日期:2024-06-30 发布日期:2024-06-30
通讯作者: 孙娜, 舒朋华

Unveiling the antiviral mechanism of Forsythia suspensa: A comprehensive analysis of screening targets and components

Na Sun^*(), Shuo Ma, Linxuan Jin, Xin Zhang, Miao Zhou, Huanhuan Yang, Wenqian Li, Xinru Wu, Yanyan Hou, Yuhan Yuan, Yu Zhang, Penghua Shu^*()

Food and Pharmacy College, Xuchang University, Xuchang 461000, Henan, China

Received:2023-11-13 Revised:2024-01-12 Accepted:2024-03-05 Online:2024-06-30 Published:2024-06-30
Contact: Na Sun, Penghua Shu
Supported by:
National Natural Science Foundation of China (Grant No. 21702178), Project of Science and Technology Department of Henan Province (Grant No. 242102310503), Postgraduate Education Reform and Quality (Grant No. YJS2023AL082), Graduate Education Reform Project of Henan Province (Grant No. 2023SJGLX294Y), the Training Plan of Young Backbone Teachers in Universities of Henan Province (Grant No. 2021GGJS144), the Key Scientific Research Program in Universities of Henan Province (Grant No. 23A350012), the National Undergraduate Training Program for Innovation and Entrepreneurship (Grant No. 202310480020 and 202410480007), School-land Cooperation Project (Grant No. 2023HX181) and Training Plan of Young Backbone Teachers in Secondary College of Xuchang University (2023).

摘要/Abstract

摘要：

连翘作为传统中药, 具有显著的抗病毒作用, 尤其是在治疗新冠肺炎方面。然而, 其抗病毒有效化合物及其靶点尚不清楚。本论文利用网络药理学技术筛选连翘中的抗病毒成分和靶标, 并利用分子对接技术分析了它们之间的相互作用。最终, 从连翘中筛选出11个活性化合物(1–11)和7个抗病毒靶标(AKT1、TP53、MYC、PTEN、CASP8、MMP9和VEGFA), 并利用基因本体论分析预测了潜在靶标可能的生物信号通路。基于分子对接结果, 我们讨论了活性化合物的构效关系。此外, 对活性化合物的吸收、分布、代谢、排泄和毒性(ADMET)特性进行了预测和分析。本研究阐明了连翘多个靶点和途径在治疗病毒性疾病中的协同作用, 以及活性化合物的可药用性。本研究为开发和设计新型抗病毒药物提供了依据。

关键词: 连翘, 抗病毒, 中药靶点, 活性成分

Abstract:

Forsythia suspensa, a traditional Chinese medicine, exhibits notable antiviral effects, particularly in the context of treating COVID-19. Despite its efficacy, the specific antiviral compounds within F. suspensa and their respective targets have not been elucidated. In this study, network pharmacology techniques were employed to identify antiviral components and targets in F. suspensa, with subsequent analysis of their interactions via molecular docking. Ultimately, 11 active compounds (1–11) and seven antiviral targets (AKT1, TP53, MYC, PTEN, CASP8, MMP9, and VEGFA) were successfully screened. Gene ontology analysis was then employed to predict potential biological signaling pathways associated with these targets. The structure-activity relationship of the active compounds was discussed based on molecular docking results. Additionally, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the active compounds were predicted and analyzed. This study not only highlighted the synergistic effects of multiple targets and pathways within F. suspensa for treating viral diseases but also underscored the druggability of its active compounds. The findings presented here laid a foundation for the development and design of novel antiviral drugs.

Key words: Forsythia suspensa (Thunb.) Vahl, Antiviral, Traditional Chinese medicine targets, Active compounds

Supporting: /attached/file/20240707/20240707164630_166.pdf

孙娜, 马烁, 靳琳萱, 张新, 周苗, 杨欢欢, 李文倩, 吴欣茹, 侯艳艳, 袁宇涵, 张玉, 舒朋华. 基于靶点和活性成分的筛选探讨连翘抗病毒作用机制[J]. 中国药学(英文版), 2024, 33(6): 543-558.

Na Sun, Shuo Ma, Linxuan Jin, Xin Zhang, Miao Zhou, Huanhuan Yang, Wenqian Li, Xinru Wu, Yanyan Hou, Yuhan Yuan, Yu Zhang, Penghua Shu. Unveiling the antiviral mechanism of Forsythia suspensa: A comprehensive analysis of screening targets and components[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(6): 543-558.

图/表 15

Table 1. The compounds screened out in the TCM database.

Figure 1. Active compounds screened from F. suspensa.

Figure 2. Venn diagram of F. suspensa targets and virus targets.

Figure 3. Active compounds‑target genes network of F. suspensa.

Figure 4. (A) PPI network of F. suspensa and virus-related target genes; (B) PPI network of the screened key target genes.

Figure 5. GO terms of 130 potential targets. The top 10 GO functional terms were selected (P ≤ 0.05). Note: The color of terms turned from blue to red. The redder the bar was, the smaller the adjusted P-value was. Abbreviations: BP: biological processes; CC: cellular component; MF: molecular function.

Figure 6. KEGG pathway enrichment of 130 potential targets. The top 20 pathways were identified. Color represented the P-value, and the size of the spot represented the count of genes.

Table 2. The data of the top 20 KEGG pathways.

Figure 7. Interaction network between active compounds and core target proteins.

Figure 8. The histograms of relative scoring percentages for compounds docking with AKT1 (A), TP53 (B), MYC (C), and PTEN (D), respectively.

Figure 9. The histograms of relative scoring percentages for compounds docking with CASP8 (A), MMP9 (B), and VEGFA (C), respectively.

Figure 10. (A) Docking and binding pattern of compound 5 (pink) into AKT1 active site; (B) 2D interaction diagram of compound 5 (pink) with amino acid residues of AKT1; (C) Docking and binding pattern of compound 5 (pink) into MMP9 active site; (D) 2D interaction diagram of compound 5 (pink) with amino acid residues of MMP9.

Figure 11. (A) Docking and binding pattern of compound 4 (blue) into PTEN active site; (B) 2D interaction diagram of compound 4 (blue) with amino acid residues of PTEN; (C) Docking and binding pattern of compound 7 (yellow) into MYC active site; (D) 2D interaction diagram of compound 7 (yellow) with amino acid residues of MYC.

Figure 12. Physicochemical property of compound 5.

Table 3. ADMET prediction results of compounds 1–11.

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基于靶点和活性成分的筛选探讨连翘抗病毒作用机制

Unveiling the antiviral mechanism of Forsythia suspensa: A comprehensive analysis of screening targets and components

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