Nirmatrelvir, A COVID-19 Drug, and Human Serum Albumin: Computational Analysis of Their Molecular Interactions

Understanding the interaction between drugs and human serum albumin (HSA) is crucial for drug development. This study investigates the binding of a COVID-19 drug, nirmatrelvir (NIR), to HSA through a computational approach. Molecular docking was employed to identify potential NIR binding site on HSA, and revealed distinct clusters at Sites I, II, and III. However, Site III exhibited a preference for NIR based on the lowest binding energy. Molecular dynamics simulation over 100 ns confirmed the stability of the NIR-HSA complex, with consistent binding at Site III. The compactness of HSA was maintained throughout the simulation period, as indicated by the radius of gyration, while structural flexibility analysis revealed typical fluctuations around some residues. Root-mean-square deviation (RMSD) patterns illustrated stability of the complex, and hydrogen bond analysis suggested four stable hydrogen bonds between NIR and HSA. These investigations offer insightful information on molecular interactions governing the stability of the NIR-HSA complex. The Site III of HSA was concluded as the favourite binding site of NIR. Among all three binding sites, lowest binding energy was shown at Site III. Hydrogen bonds and hydrophobic forces were predicted as the stabilizing forces. In a nut shell, MD simulation confirmed the stability of NIR-HSA complex. image