Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has infected millions worldwide, exacerbating global health concerns. However, a dire need for alternative therapies like active ingredients from natural sources. Therefore, QKC, which are active compounds, are being investigated from Maxing Shigan Decoction (MXSGD), a traditional Chinese medicine (TCM) formula widely used for respiratory illnesses and have shown therapeutic potential in treating SARS-CoV-2. This study investigates MXSGD's active compounds, therapeutic proteins, and pharmacological mechanisms. Integrated multiple networking and GO/KEGG pathway enrichment analysis approaches were employed. While individual ingredient effects were studied, the combined efficacy and molecular mechanisms require further exploration. By combination, quercetin-kaempferol (QKC) is hypothesized to be more effective. A systematic pharmacological approach was used to identify compound targets, predict potential targets, and conduct networking analyses. Five networks were constructed and analyzed: (a) compound-known targets, (b) compound-potential targets, (c) QKC-HP PPI, (d) QKC-MH PPI, and (e) QKC-SARS-CoV-2-PPI networks. GO and pathway enrichment analyses revealed that the ingredients target various biological processes and pathways, with QKC combining the properties of quercetin and kaempferol. This study provides valuable insights in comparing quercetin, kaempferol, and QKC and those exploring QKC's synergies and molecular mechanisms for treating SARS-CoV-2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00515-1.