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Crystal structure of Selzentry maraviroc-bound HIV-1 co-receptor CC chemokine receptor 5 (CCR5; CD195)

The crystal structure of HIV-1 co-receptor CCR5 bound by the allosteric inhibitor Selzentry maraviroc could help to guide design of therapies for HIV-1 infection. The crystal structure of the complex was determined at
2.7 Å resolution and showed Selzentry bound at a site distinct from proposed recognition sites for chemokines and HIV gp120. Crystal structure-based modeling showed that different charge distributions and steric hindrances in the co-receptor ligand-binding pocket could be major determinants for HIV-1 co-receptor selectivity. Next steps include structural studies of CCR5 and CXC chemokine receptor 4 (CXCR4; NPY3R) in complex with the HIV envelope protein gp120 and CD4 to obtain more insight into the process of viral infection.
Selzentry is marketed by Pfizer Inc. to treat HIV/AIDS.
CytoDyn Inc.'s CCR5 inhibitor, PRO 140, is in Phase II trials.
Tobira Therapeutics Inc. has the dual CCR5 and CCR2 (CD192) antagonist cenicriviroc in Phase II trials to treat HIV/AIDS. (see Seeing CCR5, page 11)

SciBX 6(39); doi:10.1038/scibx.2013.1110
Published online Oct. 10, 2013

Unpatented; licensing status not applicable

Tan, Q. et al. Science; published online Sept. 12, 2013;
Contact: Beili Wu, Shanghai Institute of Materia Medica, Chinese Academy of Sciences,
Shanghai, China