Expert Opinion on Investigational Drugs vol:14 issue:10 pages:1199-1212
Perhaps one of the most effective approaches to prevent and inhibit viral infections is to block host cell receptors that are used by viruses to gain cell entry. Major advances have been made over the past decade in the understanding of the molecular mechanism of HIV entry into target cells. A crucial step in this entry process is the interaction of the external HIV envelope glycoprotein, gp120, with the cellular CD4 receptor molecule. This binding step represents a potential target for new antiviral agents, and current efforts to develop safe and effective HIV entry inhibitors are focused on natural ligands and/or monoclonal antibodies that interfere with gp120/CD4 interaction. Also, small synthetic compounds obtained either by high-throughput screening of large compound libraries or by structure-guided rational design have recently entered the antiretroviral arena. In this review, the anti-HIV activity of novel entry inhibitors targeting gp120/CD4 interaction is outlined, and special attention is given to the cyclotriazadisulfonamide compounds, which are the most specific CD4-targeted antiviral drugs described so far.