Insights into the binding properties of calf thymus DNA with lopinavir from spectroscopic and computational studies

Lopinavir (LPV), an important antiviral drug, can inhibit effectively wild type and mutant HIV protease. In this work, molecular interaction mechanism between LPV and calf thymus deoxyribonucleic acid (ct-DNA) was characterized by spectroscopic, viscosity and molecular docking approaches to attain some important information about the LPV-ct-DNA interaction including binding affinity, binding mode, main driving-forces and structural change of ct-DNA. UV-vis titration data demonstrated that the LPV-ct-DNA complex was formed, and the binding affinity under the studied conditions was weak due to the binding constant at the level of 10(3) M-1. The negative values of Delta H-0 (-26.63 kJ.mol(-1)) and Delta S-0 (-24.11 J.mol(-1).K-1) revealed that hydrogen bonding and Van der Waals forces played an indispensable part in the LPV-ct-DNA complexation process. The outcomes from viscosity measurements excluded the possibility of intercalation mode between LPV and ct-DNA. The results from UV-vis titration experiments, displacement experiments and influence of ionic strength indicated that LPV bound to the minor groove of ct-DNA, which was further confirmed by docking studies. Besides, a minor change in the conformation of ct-DNA can be observed from CD spectral analysis. Our studies scientifically elucidated the binding behavior between LPV and ct-DNA for the first time and were beneficial to assessing the pharmacological properties of this antiviral drug. (C) 2021 Elsevier B.V. All rights reserved.