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Activation of silent biosynthetic gene clusters and profiling of secondary metabolites secreted by Endophytic Fungi for use as potential anti-HIV agents.

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The continuous burden of Human Immunodeficiency Virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated five endophytic fungi isolated from Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Single-round fractionated extracts of treated P.chrysogenum showed potent anti-HIV activity with an IC₅₀ of 5.90 μg/mL and a 5-fold increase compared to the untreated fraction. The active fractionated extracts were subjected to gas chromatography-mass spectrometry (GCMS), and more bioactive compounds were detected in treated P.chrysogenum fractions than in untreated fractions. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites as therapeutic compounds


Masters Degree. University of KwaZulu-Natal, Durban.