Computational analysis of Elongation Factor 2 (EF-2) of Cryptosporidium parvum for identification of therapeutics

Cryptosporidium parvum (Cp) is an obligate intracellular apicomplexan parasite that infects the intestinal tract of mammals. C. parvum oocysts are transmitted mainly through contact with contaminated water and then reproduce sexually and asexually in the intestinal lining cells, resulting in diarrhea. Elongation Factor 2 (EF-2) of C. parvum is a ubiquitous eukaryotic protein that is essential for protein synthesis and is regarded as a drug target for therapeutic intervention. EF-2 catalyses the translocation of peptidyl-tRNA from the amino-acyl site to the peptidyl site of the ribosome during the elongation phase of protein synthesis. In this study, the sequence similarity between the template structures and the EF-2 protein of C. parvum was considered for the determination of the three-dimensional structure of the target protein through the homology modelling approach by MODELLER v9.21 software. By using different computer-aided drug designing techniques such as structure and ligand-based studies, the potential inhibitor molecules were enlisted. Compounds like CHEMBL1784973 and ZINC_03830706 are reported as the best inhibitors against the CpEF-2 protein. Furthermore, the reliability of the binding mode of the hit molecule ZINC_03830706 is validated through a complex MD simulation study for a time frame of 100 ns in an aqueous environment. The compound identified from the computational approach can be considered through experimental studies in the future.