In silico approach of bioactive molecule chitosan 501.1 kDa from snail shell as antioxidant and inhibitor of the keap1-nrf2 protein-protein interaction

Background: ROS are created when high levels of oxidative stress occur due to hypercholesterolemia. Nuclear Factor Erythroid 2-related factor (NRF2) controls the expression of antioxidant genes. Kelch-like ECH-associated protein 1 (KEAP1) therapy degrades NRF2. Chitosan 501.1 kDa from snail shells contains bioactive chemicals that can induce NRF2 activity. Objective: To evaluate the potential antioxidant activity of the bioactive compound in Mw 501.1 kDa chitosan by targeting KEAP1 and NRF2 proteins in-silico. Method: The 3D structures of the bioactive compounds chitosan and control 51M were derived from the PubChem database, and the proteins were derived from the RCSB PDB. The biological activity of chitosan bioactive compounds was predicted using the PASS Online server. Molecular docking was performed using Hex 8.0.0 Cuda with Shape+Electro+DARS and visualised with Discovery Studio. The biological activity of chitosan compounds was predicted as lipotropic and antioxidant. Result: The discovery of the bioactive compound chitosan 501.1 kDa interacted strongly with KEAP1. The bioactive compound chitosan also inhibited KEAP1 through residues GLN75 and LEU84 at the 51M-KEAP1 interaction. Conclusion: The bioactive compound chitosan 501.1 kDa could inhibit the interaction of KEAP1-NRF2 proteins so that NRF2 could transcribe antioxidant genes. Therefore, may serve as a suitable alternative.