Oligonucleotides as inhibitors of human immunodeficiency virus.
Inhibition of human immunodeficiency virus (HIV) replication by oligonucleotides is a complex process and may be implemented by an array of antiviral mechanisms. These include inhibition of virus adsorption to the host cell, inhibition of transcription via antisense or as the result of triple helix formation, and inhibition of viral encoded enzymes such as reverse transcriptase and integrase. Since the particular mechanism of HIV inhibition depends on the oligonucleotide (ON) sequence and the ON chemical modifications, the design and synthesis of potent HIV inhibitors has been an important and rewarding focus of ON research. In this era of great concern that HIV may rapidly display resistance to any antiviral compound with one mechanism of viral inhibition, oligonucleotides are potentially attractive alternatives for therapy. Several ONs have entered clinical evaluation in AIDS patients. At present Zintevir, which inhibits both HIV adsorption and HIV integrase, is in phase I/II clinical trials.
Field
A K
AK
Department of Pharmacology and Toxicology, University of Massachusetts Medical Center, Worcester 01655, USA. akfield@erols.com
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000327:Adsorption / Q000187:drug effects; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015316:Genetic Therapy; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D009841:Oligonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000037:antagonists & inhibitors; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013873:Thionucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C107381:R 95288; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; C085909:oligonucleotide 5320; C079996:GEM91; C098172:T 30177; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; C091346:fomivirsen