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New Therapeutic Approaches Targeted at the Late Stages of the HIV-1 Replication Cycle

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Abstract:

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.





Keywords: Betulinic Acid Derivatives; Capsid; Epidemic; Gag; HIV-1; Inhibitors; Matrix; Nucleocapsid; RNA genome; UNAIDS/WHO; acyl chain; amino-acid; antiretroviral; antiviral; aromatic ring; assembly; binding affinity; bioavailability; budding; capsid antigen; causative agent; cell toxicity; covalent; cyclophilin; cytoplasmic; dimethylsuccinyl; disulfide bond; drug; drug-resistant HIV-1; encapsidation; enzymes; globular structure; glycineamide; glycoprotein; half-life; hexameric lattice; high-resolution structural; hydrophobic cavity; immunodeficiency; isolates; isoxazole; maturation; multimerization; multivesicular bodys; mutations; myristic acid; noninfectious; nucleocapsid; oxygen; peptides; phosphatidylinositol; phospholipids; polyprotein; rational drug; reduction; ribosomes; secondary screening; silicon; solubility; spectroscopy; sulfamide; tryptophan; vaccine; viral replication cycle; virology; virus infectivity; zinc-finger

Document Type: Research Article

DOI: https://doi.org/10.2174/092986711793979751

Publication date: 2011-01-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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