Preclinical discovery and development of maraviroc for the treatment of HIV.
BACKGROUND
Maraviroc is a first-in-class antiretroviral (ARV) drug acting on a host cell target (CCR5), which blocks the entry of the HIV virus into the cell. Maraviroc is currently indicated for combination ARV treatment in adults infected only with CCR5-tropic HIV-1.


METHODS
This drug discovery case history focuses on the key studies that led to the discovery and approval of maraviroc, as well as on post-launch clinical reports. The article is based on the data reported in published preclinical and clinical studies, conference posters and on drug package data.


CONCLUSIONS
The profound understanding of HIV's entry mechanisms has provided a strong biological rationale for targeting the chemokine receptor CCR5. The CCR5-antagonist mariviroc, with its unique mode of action and excellent safety profile, is an important therapeutic option for HIV patients. In general, the authors believe that targeting host factors is a useful approach for combating new and re-emerging transmissible diseases, as well as pathogens that easily become resistant to common antiviral drugs. Maraviroc, offering a potent and safe cellular receptor-mediated pharmacological response to HIV, has paved the way for the development of a new generation of host-targeting antivirals.
University of Belgrade, Institute of Nuclear Sciences VINCA, Center for Multidisciplinary Research , P.O. Box 522, Belgrade , Serbia +381 11 3408154 ; + 381 11 7440100 ; nevenav@vinca.rs.
Nevena
N
Veljkovic
Jelica
J
Vucicevic
Sabrina
S
Tassini
Sanja
S
Glisic
Veljko
V
Veljkovic
Marco
M
Radi
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017277:Drug Approval; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D000077592:Maraviroc; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc
CCR5-receptor antagonist; HIV-1; antiretroviral therapy; entry inhibitor; maraviroc