Therapeutic strategies underpinning the development of novel techniques for the treatment of HIV infection

Abstract

The HIV replication cycle offers multiple targets for chemotherapeutic intervention, including the viral exterior envelope glycoprotein, gp120; viral co-receptors CXCR4 and CCR5; transmembrane glycoprotein, gp41; integrase; reverse transcriptase; protease and so on. Most currently used anti-HIV drugs are reverse transcriptase inhibitors or protease inhibitors. The expanding application of simulation to drug design combined with experimental techniques have developed a large amount of novel inhibitors that interact specifically with targets besides transcriptase and protease. This review presents details of the anti-HIV inhibitors discovered with computer-aided approaches and provides an overview of the recent five-year achievements in the treatment of HIV infection and the application of computational methods to current drug design.

FIGURE 1

The reproductive cycle of HIV. (a) Attachment. HIV attaches to CD4 and a chemokine receptor on the surface of a T cell. (b) Fusion. The virus fuses with the cell membrane and releases the virion core into the host cell. (c) Reverse transcription. The HIV enzyme called reverse transcriptase converts the single-stranded viral RNA to double-stranded viral DNA. (d) Integration. The viral DNA is integrated into cellular DNA by the HIV enzyme integrase. (e) Transcription. The virus uses the host enzyme RNA polymerase to create copies of the HIV genomic material and messenger RNA (mRNA). The mRNA is then used to produce long chains of viral proteins. (f) Regulator protein. These are essential for the HIV viral cycle because they dramatically increase HIV gene expression. (g) Assembly. The HIV enzyme protease hydrolyzes the long chains of viral proteins into functional small proteins. New virions are then assembled with the small viral proteins an d RNA. (h) Budding. The newly assembled virions use the cellular envelope as cover and bud off from the host cell.

FIGURE 2

Structures of NeoR6 and Neo-r9.