HIV entry and fusion inhibitors.
Human immunodeficiency virus (HIV) is a retrovirus that is the causative agent of acquired immunodeficiency syndrome (AIDS). Current HIV therapy is based on targeting two critical enzymes in the viral replication machinery: reverse transcriptase and a virally encoded protease. Although mortality rates due to HIV infection have been dramatically reduced, AIDS remains a major health problem throughout the world. The emergence of HIV variants that are resistant to current therapies and potential toxicity associated with their chronic use has highlighted the need for new approaches to HIV inhibition. Identification of the mechanisms underlying viral entry into the host cell has provided a number of novel therapeutic targets and the first of these HIV fusion inhibitors (enfuvirtide [pentafuside, T-20, Fuzeon; Roche Laboratories and Trimeris]) has recently been approved in the US and Europe. This review will focus on recent progress in the development of therapeutics that target the HIV entry process.
Chantry
David
D
ICOS Corporation, Bothell, WA 98290, USA. david.chantry@arraybiopharma.com
D020816:Amino Acid Motifs / Q000187:drug effects; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D000882:Haplorhini; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000502:physiology; D009930:Organic Chemicals / Q000494:pharmacology / Q000627:therapeutic use; D010091:Oximes; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013141:Spiro Compounds / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D003497:Cyclic N-Oxides; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D008562:Membrane Glycoproteins; C502183:ONO 4128; D009930:Organic Chemicals; D010091:Oximes; D010446:Peptide Fragments; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; C502184:UK 457,758; C053512:glycoprotein 41; D000077560:Enfuvirtide; C438583:Ancriviroc; C486781:vicriviroc