In silico Evaluation of Bioactive Compounds from Endophytic Fungus Nigrospora oryzae UILRZ1 as Potential Inhibitors of Targets in Resistant Bacteria

• Nigrospora oryzae UILRZ1 is a reservoir of potent bioactive compounds. • γ-tocopherol demonstrates effective inhibitory activity against bacterial proteins. • In silico docking reveals bioactive compounds with favorable binding and stability. • S. aureus and E. faecalis protein targets are susceptible to all bioactive compounds. The widespread use of antibiotics have led to an increase in hospital-acquired infections. The prevalence of these infections led to a renewed interest in exploring bioactive compounds from sources such as endophytic fungi. Thus, this study aimed to utilize in silico methods to evaluate the antibacterial activity of γ-tocopherol, α-amyrin and 3β-acetoxy-5-bisnorcholenic acid obtained from endophytic Nigrospora oryzae UILRZ1 as potential inhibitors of clinically relevant resistant bacteria. In this study, we used protein targets in the three-dimensional form, including tyrosyl-tRNA synthetase, DNA gyrase, SHV-1 β-lactamase, penicillin-binding proteins, topoisomerase, and dihydrofolate reductase. The UniProt database was used to retrieve the targets while Glide’s Protein Wizard was used for the preparation. γ-tocopherols, 3BA5BA, and α-amyrin were the ligands obtained from the PubChem database. SiteMap was chosen for binding site prediction and Schrödinger’s Glide software was employed for molecular docking. Lipinski’s Rule of Five was used to evaluate the pharmacokinetic and pharmacodynamic properties of the ligands. The results showed that the amino acids were stable and specific based on their binding affinity. γ-tocopherol (–5.434 kcal/mol) showed the strongest affinity, making it a promising candidate for the development of novel antibiotics that are effective against resistant pathogens. The findings highlight that the identified bioactive compounds can be obtained from Nigrospora oryzae and exhibit promising antibacterial activity that can be further explored in future studies. The results also have implications for the discovery of novel derivatives from endophytic fungi for addressing antibiotic resistance.