Investigation of the Effects of Lycorine and Galanthamine Extracted from Galanthus elwesii on Viral and Parasitic Targets: An In-Silico Analysis and DFT Study

Abstract

: In this study, Density Functional Theory (DFT), ADME property analysis, and molecular docking simulations were employed to evaluate the electronic structure, antiviral potential, and antiparasitic effects of lycorine and galanthamine, two alkaloids extracted from Galanthus elwesii. DFT calculations revealed that lycorine has a lower e_gap compared to galanthamine, suggesting higher reactivity and lower stability, enhancing its potential as a drug candidate. Pharmacokinetic profiling indicated that galanthamine (TPSA: 41.93 Ų, logP: 0.797) has a lower total polar surface area (TPSA) and higher lipophilicity (logP) compared to lycorine (TPSA: 62.16 Ų, logP: -0.268), indicating that galanthamine may possess superior absorption and permeability characteristics. ADME analysis also identified galanthamine as having a lower AMES toxicity score, implying reduced mutagenic risk. A total of nine target proteins, representing viral and parasitic diseases Zika virus, malaria, leishmaniasis, and dengue, were chosen for molecular docking. Molecular docking studies demonstrated that lycorine exhibited superior binding interactions (-8.76 kcal/mol), particularly against Leishmania, and displayed stronger binding affinity across all selected target proteins. Despite galanthamine's lower toxicity profile, lycorine’s enhanced reactivity and stronger binding properties suggest its higher efficacy as a therapeutic candidate based on DFT and molecular docking results, while galanthamine shows potential based on its favourable ADME profile.