Molecular Docking Study for Prediction of Chiral HPLC Separation of Hydroxychloroquine as an Alternative Antiviral of SARS-CoV-2

Abstract

The HPLC chiral separation of hydroxychloroquine (HCQ) using chiral α-1-acid glycoprotein (AGP) column has been predicted based on a molecular docking approach. The research begins with the geometrical optimization of the HCQ compound using the quantum calculation method of semiempirical (SE) of PM6, AM1, and PM3, and Hartree-Fock (HF) and density functional theory (DFT/B3LYP) with the basis set of 3-21G, 6-31G, and 6-311G. Molecular docking was performed with AutoDock Vina and PyRx applications on exhaustiveness of 264. Redocking with AutoDock Vina was done using coordinates of X = 13.584; Y = 1.47; Z = 18.451 with a grid box size of 40 x 40 x 40 and a grid Spacing of 0.375 Å, followed by specific docking process using the same conditions as redocking. The DFT method with the basis set of 6-311G was the best calculation method because it gives the lowest PRESS and closest r2 value to one for the comparison between calculated and experimental data of 1H-NMR. The docking result shows that R-HCQ enantiomer has more negative value of binding energy and more diverse interactions in the inclusion complex, indicating that R-HCQ forms more stable complex with AGP, and therefore it will be retained longer in the AGP column and eluted from the column later after R-HCQ.