Grazia E Graham
Conference 2022 Poster Presentation
Targetting wolbachia ferrochelatase for potential drug target against filarial infections
Authors and Affiliations
Cephas Ekow Biney 1, Grazia Edumaba Graham 1, Ebenezer Asiedu 2, Dr. Alexander Kwarteng 1,2
1. Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
2. Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
Filarial infections are one of the world’s most disturbing diseases caused by 3 major parasitic worms; Onchocerca volvulus, Wuchereria bancrofti, and Brugia malayi, affecting more than 500 million people worldwide. Currently used drugs for mass drug administration in affected areas are Ivermectin, Albendazole, and Diethylcarbamazine. However, these drugs though effective have certain limitations and complications associated with their use. In addition, these parasitic worms have the tendency to develop resistance to the drugs, hence the need to discover novel drugs in eliminating these infections.
Since there is no crystallographic structure for the Wolbachia ferrochelatase (wferro), the structure was generated computationally using its protein sequence data. The ligand library, comprising of drugs from various drug banks were obtained from the ZINC database. Virtual Screening was performed with the PyRx v0.8. The evolutionary relatedness of wferro to other filarial nematodes and other species was determined in this step, using the Cluster Omega Tool. The binding energy of the ligands was calculated using the Molecular Mechanics with Poisson-Boltzmann Surface Area (MM-PBSA) analysis. Molecular dynamics simulation of the complexes was performed using GROMACS 2020.330 and CHARMM36 force field31.
Four drug candidates; Nilotinib, Ledipasvir, PubChem ID 2344 and PubChem ID c07940 were found to be ideal in competing with the enzyme’s natural substrate, Protoporphyrin IX (PP9).
This study which involved targeting enzymes in biosynthetic pathways of the parasitic worms’ endosymbiont (Wolbachia), has proven to be an alternative therapeutic option leading to the discovery of new drugs which will help facilitate the elimination of parasitic infections.