Abstract
Human Immunodeficiency Virus (HIV) remains a public health issue globally, with over 39.9 million individuals living with HIV. Despite the advancements made in the disease management through the development of antiretroviral therapies, challenges such as viral latency and the emergence of drug-resistant HIV mutant strains underscore the urgent need to alternative therapeutic agents. Natural products derived from filamentous fungi represent an untapped source in drug discovery. This study investigated the genomic and metabolomic potential of Penicillium rubens to produce secondary metabolites with anti-HIV activity. Using combined omics such as genome mining by fungiSMASH and untargeted metabolomics by Liquid Chromatography- Mass Spectrometry (LC-MS), over 52 biosynthetic gene clusters (BGCs) were identified, many of which have hypothetical functions, indicating potential novelty. Key bioactive metabolites identified included lithospermic acid, a previously reported compound found to have anti-HIV activity. Furthermore, molecular docking simulations revealed the strong binding affinities between these compounds and HIV-1 integrase, a pivotal enzyme in the HIV life cycle, suggesting pharmacological relevance. This study demonstrates the vast bioactive potential of P. rubens, and the findings underscore the value of integrated omics approaches in natural product drug discovery and further emphasize the potential of P. rubens as a promising source of pharmacologically relevant compounds.