In silico Characterization of an Initiation Factor 2 Kinase of Black Fungi: A Potential Drug Target for Mycosis

Abstract

Fungi infections are responsible for more than 1.6 million deaths per year worldwide. Treatment is time-consuming, compromising the kidney and liver functions. in silico analyses have facilitated the discovery of new drugs that may present fewer side effects. In this connection, kinases that phosphorylate the translation initiation factor eIF-2 are candidate proteins for potent new drugs, which have been recognized as important in maintaining protein synthesis. Substances that interfere with the phosphorylation of the eIF2α factor may be the way to inhibit the production of proteins and accelerate the fungi's death. To determine whether this enzyme can be used as a new drug target, this study aimed to perform in silico functional annotation and characterization of eIF2 factor kinase´s three-dimensional structure from three species of black fungi. In addition, inhibitors that could interact and bind to the active site of the enzyme were explored. The hypothetical protein was submitted to the databases and bioinformatics tools for its characterization, whose analysis of protein-protein interactions was modeled and inhibitors anchored. Protein interaction analysis linked the kinases with other molecules in protein translation and ribosome recycling. However, centrality analysis showed only one kinase as a possible drug target. The inhibitors showed coupling with the active site of protein kinases, and these results indicate a possible blockade of the enzymatic function that can accelerate the response to the drugs. This study demonstrates that biochemical characterization and in silico validation studies of potential drugs can be more efficient and yield faster results.