Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes
Michael Roche, Katharina Borm, Jacqueline K Flynn, Sharon R Lewin, Melissa J Churchill, Paul R Gorry
CURRENT TOPICS IN MEDICINAL CHEMISTRY | BENTHAM SCIENCE PUBL LTD | Published : 2016
Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-..View full abstract
MR is the recipient of an Australian NHMRC Postdoctoral Training Fellowship. PRG is supported by an Australian Research Council (ARC) Future Fellowship (FT2). SRL is the recipient of a NHMRC Practitioner Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.