Targeting peptide based therapeutics: Integrated computational and experimental studies of autophagic regulation in host-parasite interaction

ChemMedChem. 2024 Feb 5:e202300679. doi: 10.1002/cmdc.202300679. Online ahead of print.ABSTRACTCutaneous leishmaniasis caused by the intracellular parasite Leishmania major, exhibits significant public health challenge worldwide. Present study manifests the crucial role of ATG8 protein as a potential target for combating L. major infection. Using bioinformatics analysis, we identified non-conserved motifs within the ATG8 in L. major. Subsequently, a peptide library was generated based on these motifs, and three peptides were selected for further investigation through molecular docking and molecular dynamics simulations. Surface Plasmon Resonance (SPR) experiments confirmed the direct interaction between ATG8 and the identified peptides. Remarkably, these peptides demonstrated the ability to cross the parasite membrane and exert profound effects on L. major. Peptide treatment significantly impacted parasite survival, inducing alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, indicating their involvement in autophagy regulation within L. major. In vitro studies revealed that the selected peptides effectively decreased the parasite load within the infected host cells. Encouragingly, in vivo experiments corroborated these findings, demonstrating a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3I...
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research