Recent advances of CCR5 antagonists

PURPOSE OF REVIEW: The interaction of the beta-chemokine receptor CCR5 with the HIV-1 envelope glycoprotein gp120 is critical for viral entry. Therefore, CCR5 seems to be a promising target for inhibition of HIV-1 replication. A number of attempts have been made to identify small-molecule CCR5 antagonists as novel antiretroviral agents. This review focuses on recent advances of CCR5 antagonists in antiviral activity, safety, and pharmacokinetics in vitro and in vivo. RECENT FINDINGS: Following the discovery of the first small-molecule CCR5 antagonist, TAK-779, a variety of molecules have been identified as novel CCR5 antagonists, such as SCH-C, vicriviroc, maraviroc, aplaviroc, TAK-220, and TAK-652. All compounds are orally bioavailable and have proved to be highly potent and selective inhibitors of CCR5 using (R5) HIV-1 replication in cell cultures. Their biochemical and pharmacokinetic profiles, however, differ. Clinical studies of three compounds (vicriviroc, maraviroc, and aplaviroc) have been performed, and considerable reduction of plasma viral load in R5 HIV-1-infected patients has been achieved. SUMMARY: CCR5 antagonists are a novel class of antiretroviral agents and they are active against a wide range of R5 HIV-1. Most of the CCR5 antagonists subjected to clinical trials are well tolerated and have shown efficacy in HIV-1-infected patients.