Recent research results have converted gp120 binders to a therapeutic option for the treatment of HIV-1 infection. A medicinal chemistry point of view

Current therapeutic armamentarium for treatment of HIV-1 Infection is based on the use of highly active antiretroviral therapy that, unfortunately, does not act as a curative remedy. Moreover, duration of the therapy often results in lack of compliance with the consequent emergence of multidrug resistance. Finally, drug toxicity issues also arise during treatments. In the attempt to achieve a curative effect, in addition to invest substantial resources in finding new anti-HIV-1 agents and in optimizing Antiviral lead compounds and drugs currently available, additional efforts should be done to deplete viral reservoir located within host CD4⁺ T cells. Gp120 Binders represent a class of compounds able to affect the interactions between viral envelope proteins and host CD4, thus avoiding virus-to-cell attachment and fusion, and the consequent viral entry into host cells. This review summarizes the efforts done in the last five years to design new gp120 Binders, that finally culminated in the approval of fostemsavir as an anti-HIV-1 drug.

CD4 mimics; Entry inhibitors; HIV-1 infection; Small molecules; Structure-activity relationships; gp120 binders.