Small molecule antagonists of chemokine receptors as emerging anti-HIV agents

HIV entry into the cell involves the presence of at least two chemokine coreceptors, the CCR5 and CXCR4 receptors. Much research by the major drug companies has ultimately been directed to the development of small molecule chemokine antagonists that inhibit virus entry into the cell and in this way constitute novel antiviral medications. The scientific and patent literature of this highly dynamic field has been reviewed, showing that a large number of highly effective lead molecules have recently been identified, and at least one compound (the bicyclam AMD3100) has entered clinical trials as a new anti-HIV pharmacological agent. An effective chemokine antagonist with antiviral properties combined with the presently available classes of antivirals (nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) and/or protease inhibitors (PIs)) may act synergistically in the treatment of the HIV infection, explaining the tremendous research efforts in this field.