New therapeutic approaches targeted at the late stages of the HIV-1 replication cycle.
Owing to the serious clinical consequences associated with acquisition of resistance to current antiretroviral drugs, discovery of new drug targets and development of novel anti-HIV-1 therapeutic agents have become a high research priority. The late stages of HIV-1 replication involve the processes of assembly, budding and maturation, and comprise several new potential therapeutic targets which have not (yet) been targeted by any of the antiretroviral drugs approved at present. The structural protein Gag plays a central role in these stages through its different regions and mature Gag proteins working in concert. In this article, we highlight a number of steps in the late stages of HIV-1 replication that represent promising targets for drug discovery. Recent progress in development of related inhibitors targeting at CA, zinc fingers of NC, p6-Tsg101 interaction, lipid rafts of plasma membrane, proteolytic cleavage sites in Gag and gp160 processing is also reviewed.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P.R. China.
Yan
Y
Jiang
Xinyong
X
Liu
Erik
E
De Clercq
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099177:Tsg101 Protein
D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015699:HIV Envelope Protein gp120; D014157:Transcription Factors; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099177:Tsg101 Protein; C514793:gp120 protein, Human immunodeficiency virus 1; C083002:p6 gag protein, Human immunodeficiency virus 1