Lead Screening for CXCR4 of the Human HIV Infection Receptor Inhibited by Traditional Chinese Medicine

Abstract

The acquired immunodeficiency syndrome (AIDS) is a serious worldwide disease caused by the human immunodeficiency virus (HIV) infection. Recent research has pointed out that the G protein-coupled chemokine receptor CXCR4 and the coreceptor C-C chemokine receptor type 5 (CCR5) are important targets for HIV infection. The traditional Chinese medicine (TCM) database has been screened for candidate compounds by simulating molecular docking and molecular dynamics against HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and diiodotyrosine are selected based on the highest docking score. The molecular dynamics is helpful in the analysis and detection of protein-ligand interactions. According to the analysis of docking poses, hydrophobic interactions, hydrogen bond variations, and the comparison of the effect on CXCR4 and CCR5, these results indicate Saussureamine C may have better effect on these two receptors. But for some considerations, diiodotyrosine could make the largest variation and may have some efficacy contrary to expectations.

Identification of Novel 2-(1 H -Indol-1-Yl)-Benzohydrazides Cxcr4 Ligands Impairing Breast Cancer Growth and Motility

“…However, various groups functionalizing the indole nucleus could yet guarantee spatial requirements for key interactions in the previously reported pharmacophore model, as shown by molecular modeling [20]. A further improvement in the definition of CXCR4 receptor was the discovery of the orally active isothiourea ligand IT1t (4), which was co-crystallized with the receptor [21,22].…”