Computational screening of potential AT1R inhibitors from Nigella sativa for diabetic-hypertensive therapy

Hypertension, frequently coexists with Type 2 diabetes mellitus, causes due to Angiotensin II. Inhibiting Angiotensin II by targeting AT1R can potentially improve hypertension-related complications in patients with T2DM. In this study, we perform an in-silico screening based on molecular docking and molecular dynamic of 305 compounds of Nigella sativa against Angiotensin-II Type1 Receptor (AT1R). Molecular docking studies were conducted to investigate the binding affinities of the selected ligands with the target receptor and compared against the Losartan (control drug). Top 5 ligands were selected based on binding affinity. Subsequently, we conducted an ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling to assess their pharmacokinetic and safety profiles. Our findings revealed two promising ligands Beta-amyrin (CID-73145) and Taraxerol (CID-92097), which exhibited strong binding affinities and favorable pharmacological profiles with no signs of acute toxicity. The molecular dynamic simulations (MD) including RMSD, RMSF, and MMGBSA binding free energy results showed that selected two ligands bind to AT1R more proficiently with good stability over 100 ns. The computational study serves as a foundational basis for subsequent laboratory and clinical research aimed at identifying selective, potent, and less toxic diabetic-hypertensive therapy targeting AT1R.