In silico anti-leishmanial potential of algal and coral compounds using molecular dynamic simulation and docking...

Leishmaniasis is a parasitic disease prevalent in subtropical and tropical regions, with limited and often toxic treatments ineffective against drug-resistant strains. This study explored 1,013 compounds from algae and corals for potential anti-leishmanial effects.

Three-dimensional structures of Leishmania major proteins, zinc leishmanolysin glycoprotein 63 (GP63), farnesyl diphosphate synthase (FPPS), and N-myristoyltransferase (NMT), as well as 389 coral compounds and 624 algal compounds, were obtained from the PubChem database. Molecular docking analysis was performed using PyRx and AutoDock Vina software for each of the three Leishmania proteins with individual protein-ligand combinations. The properties, including activity, daily carcinogenicity, and absorption, distribution, metabolism, excretion, and toxicity (ADMET), were predicted using SwissADME, Lazar, and Way2Drug tools. Using the GROMACS program, coral and algal compounds with the highest binding scores for each protein were selected for molecular dynamics (MD) simulations.

Alga-utd-01 and Coral-utd-01 exhibited strong affinity for the GP63. Additionally, Alga-utd-05 and Coral-utd-02 showed the highest binding affinity to FPPS, while the top compounds for NMT were Alga-utd-14 and Coral-utd-03. Moreover, Alga-utd-05, Alga-utd-22, and Alga-utd-16 were common algal compounds interacting with all three proteins, and Coral-utd-01, Coral-utd-02, Coral-utd-03, Coral-utd-06, and Coral-utd-12 were common coral compounds. The MD results confirmed relatively stable interactions between the proposed compounds and the three important Leishmania proteins.

The algae- and coral-derived compounds exhibited promising anti-parasitic and anti-inflammatory properties, warranting further experimental validation for leishmaniasis treatment.