The Effect of Geometrical Isomerism of 3,5-Dicaffeoylquinic Acid on Its Binding Affinity to HIV-Integrase Enzyme: A Molecular Docking Study.
A potent plant-derived HIV-1 inhibitor, 3,5-dicaffeoylquinic acid (diCQA), has been shown to undergo isomerisation upon UV exposure where the naturally occurring 3trans,5trans-diCQA isomer gives rise to the 3cis,5trans-diCQA, 3trans,5cis-diCQA, and 3cis,5cis-diCQA isomers. In this study, inhibition of HIV-1 INT by UV-induced isomers was investigated using molecular docking methods. Here, density functional theory (DFT) models were used for geometry optimization of the 3,5-diCQA isomers. The YASARA and Autodock VINA software packages were then used to determine the binding interactions between the HIV-1 INT catalytic domain and the 3,5-diCQA isomers and the Discovery Studio suite was used to visualise the interactions between the isomers and the protein. The geometrical isomers of 3,5-diCQA were all found to bind to the catalytic core domain of the INT enzyme. Moreover, thecisgeometrical isomers were found to interact with the metal cofactor of HIV-1INT, a phenomenon which has been linked to antiviral potency. Furthermore, the 3trans,5cis-diCQA isomer was also found to interact with both LYS156 and LYS159 which are important residues for viral DNA integration. The differences in binding modes of these naturally coexisting isomers may allow wider synergistic activity which may be beneficial in comparison to the activities of each individual isomer.
Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa.
Mpho M
MM
Makola
Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa.
Ian A
IA
Dubery
Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa.
Gerrit
0000-0001-5159-1806
G
Koorsen
Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa; Council for Scientific and Industrial Research (CSIR), Biosciences, Natural Products and Agroprocessing Group, Pretoria 0001, South Africa.
Paul A
0000-0002-4416-6796
PA
Steenkamp
Department of Chemistry, Faculty of Agriculture, Science and Technology, School of Mathematical and Physical Science, North-West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa; Material Science Innovation and Modelling (MaSIM) Research Focus Area, Faculty of Agriculture, Science and Technology, North-West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa.
Mwadham M
MM
Kabanda
Department of Microbiological, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa.
Louis L
LL
du Preez
Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, Johannesburg 2006, South Africa.
Ntakadzeni E
0000-0001-7390-2118
NE
Madala