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. We conducted a comprehensive study to assess the antiviral and antiparasitic potential of lycorine and galanthamine, two alkaloids whose biosynthetic production was significantly increased by zinc supplementation. DFT calculations revealed that lycorine has a lower Egap than 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 with 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 favorable ADME profile.