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<p>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 <i>Penicillium rubens</i> P03MB2, an endophytic fungus from the <i>Albizia adianthifolia</i> 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&#xa0;kcal/mol, outperforming the co-crystallized ligand ORV. This research demonstrates the potential of secondary metabolites from <i>Penicillium rubens</i> as novel anti-HIV-1 agents, offering a foundation for further developing effective antiviral therapies.</p>

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Combining an OSMAC approach and untargeted metabolomics to profile compounds exhibiting anti-HIV-1 activities in an endophytic fungus, Penicillium Rubens P03MB2

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • Neo Moloi,
  • Mothusi C. Khumalo,
  • Wonder P. Nxumalo,
  • Sphamandla E. Mtambo,
  • Nompumelelo P. Mkhwanazi,
  • Sizwe I. Ndlovu

摘要

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.