Xiaoyan Ding

Respiratory syncytial virus (RSV) is a major pathogen responsible for severe lower respiratory tract infections in infants, the elderly, and immunocompromised individuals. Because the RSV F protein mediates viral entry and 15-lipoxygenase (15-LOX) amplifies virus-induced inflammatory responses, dual targeting of these proteins may provide both antiviral and anti-inflammatory benefits. In this study, we combined computational prediction with experimental validation to identify natural dual-target inhibitors from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). A total of 13,131 natural compounds were screened by drug-likeness evaluation, molecular docking, ADME assessment, and molecular dynamics simulations, yielding 31 potential dual-target candidates with favorable drug-like properties. Among them, rhoeadine (MOL001473) maintained stable binding conformations with both targets throughout 100 ns simulations. In BEAS-2B cells, rhoeadine exhibited significant anti-RSV activity (EC50 = 1.82 µM), low cytotoxicity (IC50 = 34.50 µM), and a selectivity index (SI) of 18.97. Time-of-addition experiments suggested that rhoeadine primarily acts at the early stage of viral infection. Additionally, ELISA results indicated that rhoeadine significantly inhibited RSV-induced secretion of CCL5 and IL-6, highlighting its anti-inflammatory potential. In summary, this study identified rhoeadine as a promising natural compound with antiviral and anti-inflammatory activities against RSV. Computational analyses suggested its potential association with RSV F protein and 15-LOX, although direct target-level validation is still required.

In this study, we systematically investigated the preventive and curative effects of food‐sourced hangover liver‐protecting beverage (HLB) against alcoholic liver disease (ALD) and their multi‐target mechanisms through molecular docking, 16S rDNA sequencing, and functional assessment of the hepatic‐intestinal axis. Based on the theory of medicinal food harmony (MFH), 121 potential active components were identified from six foods, including Hovenia dulcis , chicory, and umeboshi, by UPLC‐QTOF‐MS/MS technology. HLB characteristic active components such as quercetin, catechin, and ferulic acid were verified through molecular docking. In vivo experiments showed that HLB significantly reduced serum LPS, ALT, AST, TC, and TG levels, upregulated the expression of intestinal tight junction protein (ZO‐1/Occludin), and inhibited the activation of the TLR4 (Toll‐like receptor 4)/NF‐κB/NLRP3 inflammatory axis in ALD model mice. Meanwhile, HLB restored the homeostasis of intestinal flora and the metabolism of short‐chain fatty acids (SCFAs), confirming that it synergistically ameliorated liver injury through the “flora‐SCFAs‐intestinal barrier” axis. This study reveals the molecular basis for the regulation of ALD by food‐based natural ingredients through liver – gut interactions and provides theoretical and practical basis for the development of functional beverages with both safety and multi‐target effects.

To investigate the therapeutic impact of Forsythia suspensa extract (FS) on RSV-infected mice and explore its antiviral pharmacodynamic foundations. Methods: An integrated analytical approach, combining UPLC-Q-TOF/MS with network pharmacology, was employed to analyze and identify the chemical constituents in FS, particularly those exhibiting antiviral properties against RSV. The study integrated network pharmacology and metabolomics for further analysis, and molecular docking and interaction experiments were conducted to validate the pharmacodynamic mechanisms. Finally, an RSV pneumonia mouse model was employed to evaluate the therapeutic influence of FS, including pathological and immunohistochemistry assessments. Twenty-five components in FS were identified through UPLC-Q-TOF/MS analysis. Integrated network pharmacology data revealed 43 effective components and predicted 113 potential targets of FS for anti-RSV activity. Metabolomics analysis identified 14 metabolite biomarkers closely linked to RSV-induced metabolic disruptions involving pathways. Moreover, molecular docking and Biacore experiments provided additional confirmation that FS primarily exerts its effects through compounds such as rutin, quercetin, and kaempferol. Immunohistochemistry experiments demonstrated a significant reduction in the expression of relevant proteins following FS administration, affirming its capacity to ameliorate lung inflammation induced by RSV infection through the modulation of Toll-like receptor signaling pathways. The data presented in this study illustrate that FS exerts its anti-RSV effects by regulating the Toll-like receptor signaling pathway and the arachidonic acid metabolism pathway via rutin, quercetin, and kaempferol. Furthermore, the approach of combining network pharmacology with metabolomics proves to be an effective research strategy for investigating the bioactive constituents of medicinal plants and elucidating their pharmacological effects.

Objective. Forsythia suspensa leaf (FSL) has been used as a health tea in China for centuries. Previous experiments have proved that FSL extract has a good effect on the antirespiratory syncytial virus (RSV) in vitro, but its exact mechanism is not clear. Therefore, this study aims to determine the active components and targets of FSL and further explore its anti-RSV mechanism. Methods. UPLC-Q-Exactive-MS was used to analyze the main chemical components of FSL. The compound disease target network, PPI, GO, and KEGG were used to obtain key targets and potential ways. Then, the molecular docking was verified by Schrödinger Maestro software. Next, the cell model of RSV infection was established, and the inhibitory effect of each drug on RSV was detected. Finally, western blotting was used to detect the effect of the active components of FSL on the expression of PI3K/AKT signaling pathway-related protein. Results. UPLC-Q-Exactive-MS analysis showed that there were 67 main chemical constituents in FSL, while network pharmacological analysis showed that there were 169 anti-RSV targets of the active components in FSL, involving 177 signal pathways, among which PI3K/AKT signal pathway played an important role in the anti-RSV process of FSL. The results of molecular docking showed that cryptochlorogenic acid, phillyrin, phillygenin, rutin, and rosmarinic acid had higher binding activities to TP53, STAT3, MAPK1, AKT1, and MAPK3, respectively. In vitro experiments showed that phillyrin and rosmarinic acid could effectively improve the survival rate of RSV-infected cells, increase the expression level of PI3K, and decrease the expression level of AKT. Conclusion. The active ingredients of FSL, phillyrin, and rosmarinic acid can play an anti-RSV role by inhibiting PI3K/AKT signaling pathway. This study provides reliable theoretical and experimental support for the anti-RSV treatment of FSL.