Screening Bioactive Compounds from Vietnamese Medicinal Plants as Inhibitors of CCR5 and CXCR4 Co-receptors to Prevent and Treat HIV-1 Infection by Molecular Docking Methods

Abstract

Investigation of CCR5 and CXCR4 inhibitors, the two HIV-1 co-receptors, has the potential to search for new anti-HIV-1 agents. In the present study, a virtual screening for multi-targeted CCR5 and CXCR4 inhibitors from Vietnamese natural products has been carried out using molecular docking simulations. The X-ray crystal structures of CCR5 (4mbs) and CXCR4 (3odu) have been retrieved from the Protein Data Bank as target models. A consensus docking protocol was developed using ICM and Autodock Vina packages. More than 1300 natural compounds were screened and their binding affinity was compared to that of maraviroc and ITD, two well-known inhibitors of viral CCR5 and CXCR4 targets. The results showed that 27 out of 1376 compounds were able to target viral CCR5 and CXCR4 receptors simultaneously. Among them,
1-hydroxysyringaresinol from Pseuderanthemum carruthersii and ombousid from Gynostemma pentaphyllum showed the best bioactivity profiles. Physicochemical calculations also demonstrated their suitability to be further investigated as novel anti-HIV-1 agents.