Mechanistic Insights into Shenfu Injection for COVID-19-Induced ARDS: A Combined Analysis of GEO Database, Network Pharmacology, and Molecular Docking.

Introduction: Acute respiratory distress syndrome (ARDS) is a severe and life-threatening complication of COVID-19, for which no specific antiviral treatment currently exists. Shenfu Injection (SFI), a traditional Chinese medicine formulation, has shown clinical promise in improving respiratory function and reducing mortality in ARDS patients. However, its underlying molecular mechanisms remain poorly understood.

Methods: A combined network pharmacology and bioinformatics approach was used to elucidate the potential mechanisms of SFI against COVID-19-induced ARDS. SFI-related targets were identified through multiple public databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. Gene expression data from GEO datasets (GSE171110 and GSE273149) were used to identify differentially expressed genes in COVID-19-induced ARDS, which were then intersected with SFI targets. Molecular docking was performed to evaluate the binding affinities between major active compounds in SFI and core viral proteins, including 3CLpro, RdRp, and ACE2.

Results: A total of 398 SFI-associated targets were identified, with key targets including SRC, MAPK1, MAPK3, PIK3R1, and STAT3. Active compounds such as Gomisin B, Deoxyharringtonine, Ginsenoside-Rh4_qt, Suchilactone, and Celabenzine were highlighted. Enrichment analyses identified 2,883 GO terms and 219 KEGG pathways (P < 0.05), primarily involving the PI3K-Akt, MAPK, TNF, NF-κB, and apoptosis signaling pathways. GEO data analysis confirmed the involvement of these pathways in COVID-19-induced ARDS. Molecular docking showed strong binding affinities, particularly between Ginsenoside-Rh4_qt and 3CLpro/ACE2, and Celabenzine with RdRp.

Discussion: The findings suggest that SFI exerts therapeutic effects through modulation of key inflammatory and immune pathways and by direct interaction with SARS-CoV-2 viral proteins. This multi-target mechanism aligns with the pharmacological characteristics of traditional Chinese medicine. However, further experimental validation is required to confirm these computational predictions and assess clinical relevance.

Conclusion: This study provides mechanistic insights into how SFI may alleviate COVID-19-induced ARDS via modulation of critical signaling pathways and interaction with viral targets, offering a theoretical foundation for its clinical application in the management of severe COVID-19 cases.