Virtual Screening Insights into Bag1 Inhibition: Screening of <em>Nigella sativa</em> Phytochemicals and Their Homologues

BAG1 (Bcl-2-associated athanogene 1) is a versatile protein that plays a crucial role in various cellular functions, such as the regulation of cell survival, apoptosis, and protein quality management. Unusual BAG1 expression levels have been observed in multiple cancer types. This atypical expression grants cancer cells the capability to evade cell death via both cellular processes and cancer treatments. Focusing on inhibition of BAG1 with natural compounds presents a hopeful treatment strategy. This study investigates the inhibitory potential of phytochemicals derived from Nigella sativa against BAG1 using molecular docking techniques. Initially, a comprehensive insilico screening of Nigella sativa phytochemicals was conducted to evaluate their binding affinities against BAG1. The compound exhibiting the lowest binding energy was identified as the most promising candidate, demonstrating greater selectivity for BAG1 and inhibiting its aberrant activity in the natural pathway. The most promising phytochemical was further analysed by docking its structural and functional homologues against BAG1 to assess their potential as inhibitors, aiming to identify the most suitable BAG1 inhibitor. The results revealed five compounds that can inhibit the activity of BAG1 and have a higher binding affinity towards BAG1 than its natural bound inhibitor 3F5. This study provides valuable insights into the potential of Nigella sativa-derived compounds as BAG1 inhibitors, contributing to the development of novel cancer therapeutics.