New Therapeutic Approaches Targeted at the Late Stages of the HIV-1 Replication Cycle
Yan Jiang, Xinyong Liu and Erik De Clercq
Affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P.R., China.
Keywords: HIV-1, assembly, budding, maturation, Gag, Matrix, Nucleocapsid, Capsid, immunodeficiency, causative agent, UNAIDS/WHO, Epidemic, vaccine, drug, antiretroviral, viral replication cycle, noninfectious, polyprotein, cytoplasmic, RNA genome, capsid antigen, glycoprotein, encapsidation, multimerization, hexameric lattice, mutations, zinc-finger, globular structure, virus infectivity, myristic acid, phospholipids, phosphatidylinositol, acyl chain, antiviral, ribosomes, multivesicular bodys, amino-acid, high-resolution structural, peptides, enzymes, rational drug, silicon, spectroscopy, hydrophobic cavity, isolates, Inhibitors, glycineamide, cyclophilin, oxygen, isoxazole, sulfamide, binding affinity, disulfide bond, half-life, reduction, solubility, cell toxicity, covalent, bioavailability, aromatic ring, tryptophan, secondary screening, Betulinic Acid Derivatives, dimethylsuccinyl, drug-resistant HIV-1, virology
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.
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