Targeting the zinc metalloprotease gp63 of Leishmania for vaccine design and new drug discovery using immunoinformatics, molecular docking and molecular dynamics simulation studies

Leishmaniasis is a vector-borne parasitic disease caused by Leishmania spp., for which there is no vaccine and an urgent need for better drugs. The zinc metalloprotease gp63 of Leishmania has been identified as an antigenic structure for vaccine design and a promising target for new antileishmanial agents. In this study, immunoinformatics was used to design a full vaccine construct with the cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes of gp63 from Old and New World Leishmania spp. The vaccine construct comprising of these epitopes, with suitable adjuvant and linker sequences, was found to be thermostable, highly antigenic and non-allergenic. A total of 13 linear B-cell epitopes, and 12 continuous and four discontinuous B-cell epitopes, were further identified using the BepiPred and ElliPro prediction programs, respectively. In addition, molecular docking and molecular dynamics simulation studies were performed to identify new antileishmanial molecules with the potential to target gp63. Nareline - a phytomolecule from the antileishmanial plant Alstonia scholaris - showed the best predictive binding affinity for gp63, forming stable interactions with key residues in the active site of this protein. This study highlights the promising role of gp63 in the search for new vaccines and therapeutic agents to combat leishmaniasis.