Maraviroc is a potent and selective antagonist of Chemokine Receptor CCR5 [1].
CCR5 is a receptor for chemokines and exists on the surface of white blood cells that are involved in the immune system. Many forms of HIV enter and infect host cells through CCR5 [1].
Maraviroc is a potent and selective inhibitor of CCR5 with potent anti-HIV-1 activity. Maraviroc exhibited antiviral activity against all CCR5-tropic HIV-1 viruses tested with IC90 of 2.0 nM. In HeLa P4 cells, maraviroc inhibited binding of viral envelope gp120 to CCR5 with IC50 value of 11 nM and prevented the membrane fusion events, which were necessary for viral entry. While, maraviroc didn’t affect CCR5 levels or associated intracellular signaling, which suggested it is an antagonist of CCR5 [1].
In a patient infected with both R5-tropic and X4-tropic HIV-1 viruses, treatment with maraviroc suppressed all R5-tropic viruses. And the R5-tropic viruses were replaced by more X4-tropic viruses [2].
References:
[1].? Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother, 2005, 49(11): 4721-4732.
[2].? Symons J, van Lelyveld SF, Hoepelman AI, et al. Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient. J Antimicrob Chemother, 2011, 66(4): 890-895.
