Advancement in developing a new class of anti-AIDS drugs: HIV entry inhibitors / 中国药理学通报

ABSTRACT

Process of HIV fusion with target cells, mediated by the HIV envelope glycoprotein surface subunit gp120 and the transmembrane subunit gp41, is an important step for drug intervention. The membrane fusion events leading to HIV entry into the target cell are initiated by the binding of gp120 to CD4 and subsequently to a co-receptor, CXCR4 or CCR5. Consequently, gp41 undergoes conformational changes, resulting in the fusion between the viral and cellular membranes or between the infected and uninfected cells. Therefore, gp120 and gp41 on the virions and CD4 and coreceptors on the target cells may serve as targets for development of a new class of anti-HIV drugs, HIV entry inhibitors, with a mechanism of action different from those mediated by reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs), the two classes of antiretroviral drugs approved by FDA for clinical application. The successful development of a peptidic anti-HIV drug T-20, which is targeted to the HIV gp41, implies that HIV entry inhibitors are milestone in the current anti-HIV therapy. Application of the HIV entry inhibitors alone or in combination with the RTIs and PIs will increase the efficacy and reduce the toxicity of these anti-HIV drugs and will save lives of AIDS patients who fail to response to the current antiretroviral drugs. The advancement in the study and development of the HIV entry inhibitors was reviewed here in detail