Oral CCR5 inhibitors: will they make it through?
The therapeutic armamentarium against HIV has recently gained a drug belonging to a novel class of antiretrovirals, the entry inhibitors. The last decade has driven an in-depth knowledge of the HIV entry process, unravelling the multiple engagements of the HIV envelope proteins with the cellular receptorial complex that is composed of a primary receptor (CD4) and a co-receptor (CCR5 or CXCR4). The vast majority of HIV-infected subjects exhibit biological viral variants that use CCR5 as a co-receptor. Individuals with a mutated CCR5 gene, both homo- and heterozygotes, appear to be healthy. For these and other reasons, CCR5 represents an appealing target for treatment intervention, although certain challenges can not be ignored. Promising small-molecule, orally bioavailable CCR5 antagonists are under development for the treatment of HIV-1 infection.
Biswas
Priscilla
P
San Raffaele Scientific Institute, Laboratory of Clinical Immunology, Clinic of Infectious Diseases, Via Stamira d'Ancona 20, 20127 Milan, Italy. biswas.priscilla@hsr.it
Nozza
Silvia
S
Scarlatti
Gabriella
G
Lazzarin
Adriano
A
Tambussi
Giuseppe
G
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry; D065100:CCR5 Receptor Antagonists; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015507:Drugs, Investigational; D019713:Receptors, CCR5