A computational approach to identify novel plant metabolites against Aspergillus fumigatus

Abstract

Aspergillus fumigatus, a common saprotrophic fungus is one of the most important causative agents of invasive aspergillosis. People with compromised immune systems or lung disorders are at a higher risk of acquiring Aspergillus-related health issues. The global number of invasive aspergillosis cases is expected to be over 300000 per year, with a 50 % death rate even when recognized and treated early. Current noninvasive therapies for fungal infections are azoles. As A. fumigatus resistance to azoles is rising, this study attempted to evaluate several plant metabolites as potential inhibitory agents of A. fumigatus by using in silico method. Five essential proteins including Chitinase, Glycosyl hydrolases, Glycosylphosphatidylinositol anchor, N-myristoyl transferase, and O-mannosyltransferases were selected as target proteins due to their involvement in morphogenetic processes, cell wall polysaccharides biosynthesis, filamentation, survival, organismal characteristics, proliferation, and cell wall integrity. Out of our 20 plant metabolites, four metabolites i.e., Chlorogenic acid, Protopine, Spirostanol, and Viniferin showed the best binding affinity with the key outer membrane protein of A. fumigatus during molecular docking analysis. Viniferin showed the highest binding affinity of about −262.07 and −247.63 with Chitinase and glycosyl hydrolases respectively. Molecular dynamic simulation was used to look further into the stability of the best two protein-ligand complexes. The average RMSD value of 2.4 A° for Chitinase-Viniferin and 2.2 A° for Glycosyl hydrolases-Viniferin complex demonstrated their excellent stability. ADME (absorption, distribution, metabolism, and excretion) analysis of these four plant metabolites showed that none of them had any side effects that might interfere with their drug-likeness efficiency, and no substantial toxic effects or allergenicity were also identified. Thus, all the predicted four plant metabolites can be used as a possible inhibitor of A. fumigatus. Furthermore, we strongly recommend more in vitro and in vivo trials to experimentally strengthen our encouraging outcomes.