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Panax Ginseng C.A. Meyer (PGCAM) is a well-known phytomedicine, but most of its compounds, such as ginsenoside derivatives, have poor absorption and bioavailability profile due to high molecular weight (≥500 Daltons), which is the major hurdle for their clinical application. Hence, this research explored the efficiency of low molecular weight compounds (LMWCs) (&lt;500 Daltons) screened from PGCAM and their anti-COVID-19 mechanisms through network pharmacology. Molecular compounds from PGCAM were identified using public databases and filtered out by the drug-likeness evaluation. Genes interacted with these filtered compounds, and COVID-19-related genes were extracted from public databases. In addition, overlapping genes between compounds and interactive genes were identified using the Venn diagram. In parallel, the networking between compounds and overlapping genes was analyzed by RStudio. The pathway enrichment analysis of overlapping genes was determined by STRING. Finally, the key bioactive compounds were documented through virtual screening. The bubble chart suggested that the mechanisms of PGCAM against COVID-19 were related to 28 signaling pathways. The key molecular anti-COVID-19 mechanisms might be the anti-inflammation, anti-permeability, and pro-apoptosis by inactivating the PI3K-Akt signaling pathway. The six key genes and the five compounds related to the PI3K-Akt signaling pathway were RELA-paeonol, NFKB1-frutinone A, IL6-nepetin, MCL1-ramalic acid, VEGFA-trifolirhizin, and IL2-trifolirhizin. The docking between these key genes and compounds demonstrated promising binding affinity with a good binding score. Overall, our proposed LMWCs from PGCAM provide a fundamental basis with noteworthy pharmacological evidence to support the therapeutic efficacy of PGCAM in relieving the main symptoms of COVID-19.

The Promising Mechanisms of Low Molecular Weight Compounds of Panax Ginseng C.A. Meyer in Alleviating COVID-19: A Network Pharmacology Analysis