Integrated computational biology and network pharmacology predict anti-cancer potential of the novel pteridophyte, Leucostegia immersa C. Presl, against non-small cell lung cancer

Lung cancer is the most common type of cancer and the leading cause of mortality in 2022. The development of safer alternatives from natural sources may be a potential solution to the non-specificity of conventional NSCLC therapeutics. Leucostegia immersa C. Presl of the Hypodematiaceae family is a significant medicinal fern used in the treatment of swelling, burns, and boils. However, its anti-NSCLC efficacy, specific compounds, and the mechanisms of action are unexplored to date. To address these lacunae, we have identified the phytoconstituents present in this fern and its anti-lung cancer activity, using an integrated network pharmacology and computational biology approach. In the present investigation, the cell viability of the hydroalcoholic extract of Leucostegia immersa leaf was evaluated against human lung cancer cell A549, and the extract showed anti-proliferative activity, with no significant cytotoxicity observed in the normal cell line HEK293. The LC-MS analysis of the extract detected the presence of 36 phytochemicals, and screening was conducted using ProTox 3.0. Network pharmacology, GO enrichment, and KEGG pathway analysis were utilized to detect possible targets for NSCLC. In-silico study revealed Irinotecan, Cancentrine, and Grossamide as key compounds with average binding energies -10.1, -9.0, and -8.9 kcal/mol, respectively. Out of 20 proteins, PTGS2 showed the highest affinity with an average binding energy value of -8.4 kcal/mol. The molecular dynamic simulation exhibited consistent and stable binding interactions. Therefore, the isolation of these compounds, further in vitro and in vivo experiments, may open a new avenue for anti-NSCLC drug development.