Integrated in silico pharmacology of Pleurotus ostreatus derived bioactive compounds targeting EGFR using network pharmacology and molecular simulations

From the paper

Abstract

Abstract Cancer remains a most important worldwide health burden, demanding the progress of pioneering and mechanism-driven therapeutic strategies. In this study, we employed an consolidative in silico pharmacology approach combination network pharmacology, molecular docking, ADMET profiling, and molecular dynamics simulations to examine the anticancer potential of Pleurotus ostreatus -derived bioactive compounds. Nine phytochemicals with favorable pharmacokinetic and toxicological profiles were identified, yielding 138 presumed cancer-associated targets. Protein–protein interaction (PPI) network analysis highlighted 15 key hub genes, including CASP3, EGFR, ESR1, HSP90AA1, PPARG, MDM2, PARP1, SRC, PIK3CA, RELA, JAK2, PTGS2, GSK3B, PIK3R1, and TLR4, which are judgmentally complex in multiple cancer types such as breast, colorectal, liver, and lung cancers. Functional enrichment analysis further exposed their significant engrossment in varied oncogenic signaling pathways. Among these targets, EGFR appeared as a projecting therapeutic node. Molecular docking identified lovastatin as the most promising candidate, showing strong binding affinity toward EGFR. The steadiness and interaction dynamics of the lovastatin–EGFR complex were further confirmed through molecular dynamics simulations, while ADMET analysis supported its favorable drug-likeness and safety profile. Collectively, this study highlights the potential of P. ostreatus -derived compounds, predominantly lovastatin, as multi-target anticancer agents. More importantly, it establishes the power of integrating computational and systems-level approaches to quicken the identification of novel therapeutics. Further experimental validation is acceptable to confirm these findings and enable their translational application in cancer therapy.