title: Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses.
abstract: Nucleoside antiretroviral agents are chiral small molecules that have distinct advantages compared to other classes including long intracellular half-lives, low protein binding, sustained antiviral response when a dose is missed, and ease of chemical manufacture. They mimic natural nucleosides and target a unique but complex viral polymerase that is essential for viral replication. They remain the cornerstone of highly active antiretroviral therapy (HAART) and are usually combined with non-nucleoside reverse [corrected] transcriptase and protease inhibitors to provide powerful antiviral responses to prevent or delay the emergence of drug-resistant human immunodeficiency virus (HIV). The pharmacological and virological properties of a selected group of nucleoside analogs are described. Some of the newer nucleoside analogs have a high genetic barrier to resistance development. The lessons learned are that each nucleoside analog should be treated as a unique molecule since any structural modification, including a change in the enantiomeric form, can affect metabolism, pharmacokinetics, efficacy, toxicity and resistance profile.
authors.affiliation: Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, and Veterans Affairs Medical Center, Decatur, Georgia 30033, USA. rschina@emory.edu
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: Brenda I
authors.initials: BI
authors.lastname: Hernandez-Santiago
authors.forename: Selwyn J
authors.initials: SJ
authors.lastname: Hurwitz
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides