Discovery of a Small Molecule Inhibitor of the Interaction Between HIV-1 Proteins and Cellular Cofactors: A Novel Candidate Anti-HIV-1 Drug
Abstract:Current therapeutic strategies to inhibit the replication of human immunodeficiency virus type 1 (HIV-1) use a combination of drugs targeted at the viral reverse transcriptase, protease and integrase enzymes. The clinical advantages of this combination therapy are considerable, although the emergence of drug-resistant viral strains still presents a challenge. Import of the HIV-1 viral pre-integration complex (PIC) into the nucleus is a vital step in the process of viral replication in non-dividing cells (such as terminally differentiated macrophages). The interaction between the HIV-1 accessory protein, Vpr, and the cellular protein, importin-α, is critical for nuclear import of the PIC. Targeting the protein-protein interactions involved in the regulation of HIV-1 replication might be one way to combat the continued emergence of drug-resistant HIV-1 mutants. In this review, the current status of AIDS therapy, the mechanisms involved in the nuclear import of the PIC and the discovery of a new small molecular inhibitor of HIV-1 replication are discussed.
Document Type: Research Article
Publication date: September 1, 2010
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Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).
Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).