Homology modeling, docking and molecular dynamics studies of some secondary metabolites of actinomycetes as biocontrol agents against the 3HNR enzyme of the phytopathogenic fungus .

Early blight of tomatoes is a common disease caused by the phytopathogenic fungi , in particular the species This disease causes significant losses in the tomato harvest. The enzyme 1,3,8-trihydroxynaphthalene reductase (3HNR) is a key enzyme involved in the production of melanin, that plays a crucial role in the process of fungi invasion. This enzyme is the target of some chemical fungicides, but the problem of resistance against these molecules requires the search for new molecules that are both effective and environment-friendly. Actinomycetes represent an important source of secondary metabolites with antimicrobial activity. Thus, in this study 110 secondary metabolites of actinomycetes were subjected to an in silico screening of their antifungal activity as possible inhibitors of the 3HNR of . For this reason, the 3D structure of this enzyme was modeled. Then, a molecular docking study of the secondary actinomycetal metabolites was carried out within the catalytic site of the enzyme. Indole-3-carboxylic acid, Streptokordin, 3-Phenylpropionic acid, Phenylacetate, and 8-Hydroxyquinoline have shown the most promising results with binding energies of -6.1 kcal/mol, -6.1 kcal/mol, -5.4 kcal/mol, -5.3 kcal/mol, and -5.0 kcal/mol, respectively. These metabolites have also shown satisfactory results for drug-likeness and ADMET analysis. The interaction stability of the Streptokordin, Indole-3-carboxylic acid, Phenylacetate, and 8-Hydroxyquinoline within the catalytic site of 3HNR was confirmed by the results of the MD simulation and MM-PBSA analyzes. With their favorable interactive and pharmacokinetic characteristics, these metabolites may be potential antifungal molecules against , and good candidates for further studies.Communicated by Ramaswamy H. Sarma.