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Background <p>Influenza A virus (IAV) infection poses a significant global health burden, contributing to high morbidity and mortality in both humans and animals through rapid viral transmission and dysregulated inflammatory responses. Fangqin Qinggan Decoction (FQ-01), a traditional Chinese medicine (TCM) formula, has demonstrated clinical efficacy in treating viral upper respiratory infections, however, its underlying therapeutic mechanisms remain poorly understood.</p> Methods <p>The therapeutic efficacy and mechanisms of FQ-01 against IAV infection were comprehensively investigated using a multidisciplinary approach, including in vivo murine models, histopathological (H&amp;E staining), RT-qPCR, immunohistochemistry (IHC), network pharmacology, weighted gene co-expression network analysis (WGCNA), machine learning (LASSO), transcriptomics, metabolomics, molecular docking and molecular dynamics (MD) simulation.</p> Results <p>FQ-01 significantly improved survival rates, reduced clinical mortality, and mitigated pulmonary inflammation in an IAV-infected mice while suppressing viral replication. Integrated bioinformatics and LASSO regression analyses identified 20 genes associated with FQ-01’s antiviral effects, with <i>Myd88</i> and <i>Ccl5</i> emerging as key targets. Transcriptomic profiling of murine lung tissues further validated these genes as critical mediators of FQ-01’s therapeutic action. Spearman correlation analysis revealed strong associations between <i>Myd88</i>/<i>Ccl5</i> expression and serum/lung metabolites, particularly 3-indolyl sulfate and inosine. Subsequent in vivo RT-qPCR and IHC validation, molecular docking, and MD simulations confirmed that FQ-01 exerts its anti-IAV effects by inhibiting <i>Myd88</i> and <i>Ccl5</i> expression.</p> Conclusions <p>Our findings elucidate the molecular mechanisms underlying FQ-01’s therapeutic potential against IAV infection, highlighting <i>Myd88</i> and <i>Ccl5</i> as promising targets for antiviral and anti-inflammatory interventions. This study provides a foundation for further exploration of TCM-based strategies in combating influenza and related respiratory infections.</p> Graphical Abstract <p></p>

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Deciphering the antiviral mechanisms of Fangqin Qinggan decoction against influenza A virus: a multi-omics and machine learning approach

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月5日

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  • Huan Lei,
  • Hao Zhang,
  • Yixi Xu,
  • Lianjiang Hu,
  • Bin Zhang,
  • Hao Zhou,
  • Ping Wang,
  • Simin Chen,
  • Shijun Xu

摘要

Background

Influenza A virus (IAV) infection poses a significant global health burden, contributing to high morbidity and mortality in both humans and animals through rapid viral transmission and dysregulated inflammatory responses. Fangqin Qinggan Decoction (FQ-01), a traditional Chinese medicine (TCM) formula, has demonstrated clinical efficacy in treating viral upper respiratory infections, however, its underlying therapeutic mechanisms remain poorly understood.

Methods

The therapeutic efficacy and mechanisms of FQ-01 against IAV infection were comprehensively investigated using a multidisciplinary approach, including in vivo murine models, histopathological (H&E staining), RT-qPCR, immunohistochemistry (IHC), network pharmacology, weighted gene co-expression network analysis (WGCNA), machine learning (LASSO), transcriptomics, metabolomics, molecular docking and molecular dynamics (MD) simulation.

Results

FQ-01 significantly improved survival rates, reduced clinical mortality, and mitigated pulmonary inflammation in an IAV-infected mice while suppressing viral replication. Integrated bioinformatics and LASSO regression analyses identified 20 genes associated with FQ-01’s antiviral effects, with Myd88 and Ccl5 emerging as key targets. Transcriptomic profiling of murine lung tissues further validated these genes as critical mediators of FQ-01’s therapeutic action. Spearman correlation analysis revealed strong associations between Myd88/Ccl5 expression and serum/lung metabolites, particularly 3-indolyl sulfate and inosine. Subsequent in vivo RT-qPCR and IHC validation, molecular docking, and MD simulations confirmed that FQ-01 exerts its anti-IAV effects by inhibiting Myd88 and Ccl5 expression.

Conclusions

Our findings elucidate the molecular mechanisms underlying FQ-01’s therapeutic potential against IAV infection, highlighting Myd88 and Ccl5 as promising targets for antiviral and anti-inflammatory interventions. This study provides a foundation for further exploration of TCM-based strategies in combating influenza and related respiratory infections.

Graphical Abstract