In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants

Context: Given the elusive nature of Primary Amoebic Meningoencephalitis (PAM), caused by Naegleria fowleri, early detection is vital, yet challenging due to limited clinical indicators. This research leverages Indonesia's rich biodiversity to explore novel sources of traditional medicine. Aims: To evaluate the potential compounds from Indonesian plants that possess antiamoebic and antifungal properties for inhibiting the N. fowleri CYP51 protein, crucial for cell integrity. Methods: Initially, 92 compounds were screened, and six were shortlisted following ADMETox evaluation. Subsequent steps encompassed QSAR analysis, molecular docking, and molecular dynamics simulations. Results: The QSAR analysis verified the activity potential of these six compounds, progressing them to molecular docking analysis. Among these, curcumenol from Curcuma longa emerged as a promising contender, displaying the lowest binding affinity at -9.2 kcal/mol, indicative of superior binding compared to other ligands. Molecular dynamics simulations underscored the stability of all compounds, with root mean square fluctuation (RMSF) values within 1-3 Å. Conclusions: Consequently, employing a comprehensive approach spanning ADMETox, QSAR, molecular docking, and dynamics simulations, curcumenol emerged as the prime candidate for inhibiting the N. fowleri CYP51 protein, suggesting its potential as a PAM therapeutic agent.