Combining an OSMAC approach and untargeted metabolomics to profile compounds exhibiting anti-HIV-1 activities in an endophytic fungus, Penicillium Rubens P03MB2
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Nature Research
Abstract
The persistent burden of HIV-1 in Sub-Saharan Africa underscores the need for innovative treatments, as current antiretroviral therapies cannot eliminate latent proviral reservoirs and face challenges from multidrug-resistant strains. This study investigates the potential of Penicillium rubens P03MB2, an endophytic fungus from the Albizia adianthifolia plant, as a source of novel anti-HIV-1 compounds. The fungus was cultivated in various media (malt extract broth, oats, and rice), with oat media yielding crude extracts exhibiting significant anti-HIV-1 activity. Active fractions were further analyzed using an untargeted metabolomics and molecular networking approach, revealing clusters of secondary metabolites, including coumarins and other anti-HIV-1-associated compounds. A virtual screening workflow was employed to assess the binding affinities of these metabolites against HIV-1 protease. Furthermore, molecular dynamics simulations were used to analyze ligand-protein complex stability. Binding free energy calculations highlighted diosgenin as a promising candidate, with a binding free energy of -34.59 kcal/mol, outperforming the co-crystallized ligand ORV. This research demonstrates the potential of secondary metabolites from Penicillium rubens as novel anti-HIV-1 agents, offering a foundation for further developing effective antiviral therapies.
Description
DATA AVAILABILITY : The positive Feature-Based Molecular Networking data is available at https://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=79673f544bdd4bf0b31bf915f7a5b14f. The LC-HRMS/MS metabolomics data has been deposited in Massive https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?accession=MSV000097382.
Keywords
HIV-1, Sub-Saharan Africa (SSA), Multidrug-resistant strains, Antiretroviral therapy (ART), Penicillium rubens P03MB2, Albizia adianthifolia plant, Anti-HIV-1 activity, Endophytic fungi, Human immunodeficiency virus (HIV), Secondary metabolites, Untargeted metabolomics
Sustainable Development Goals
SDG-03: Good health and well-being
Citation
Moloi, N., Khumalo, M.C., Nxumalo, W.P. et al. Combining an OSMAC approach and untargeted metabolomics to profile compounds exhibiting anti-HIV-1 activities in an endophytic fungus, Penicillium Rubens P03MB2. Scientific Reports 15, 22746: 1-18 (2025). https://doi.org/10.1038/s41598-025-08091-2.