HIV-1 Entry Inhibitors

The discovery of chemokine receptors as essential cofactors for HIV-1 entry into target cells, as well as the publication of crystal structures of viral molecules involved in the entry process, has stimulated the development of a broad spectrum of novel antiviral substances targeting this initial step in the virus replication cycle. The aim of this article is to review the antiviral compounds targeting different steps during HIV-1 entry: 1) attachment inhibitors, which block the initial binding of the virus to the cell, 2) compounds interfering with subsequent coreceptor binding, and 3) fusion inhibitors, which prevent the fusion process between viral and cellular membranes. Some of these compounds have already entered clinical phase I/II trials and are promising drugs due to their mode of action, i.e. inhibition of de novo infection of cells and their potent antiviral activity. Thus, new therapeutic options will be available to be used in combination with highly active antiretroviral therapy (HAART) to treat drug-naive, but also drug-experienced, HIV-positive persons. Furthermore, insights into the process of HIV-1 entry also stimulate new approaches for vaccine development.