Chemokine antagonists as therapeutics: focus on HIV-1.
Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. Chemokine receptor antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4 potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small-molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of concept for this novel drug class; phase III safety and efficacy trials are under way.
Tsibris
Athe M N
AM
Infectious Disease Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Kuritzkes
Daniel R
DR
D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000502:physiology
D023581:HIV Fusion Inhibitors; D019707:Receptors, Chemokine