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Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Discovery of a Small Molecule Inhibitor of the Interaction Between HIV-1 Proteins and Cellular Cofactors: A Novel Candidate Anti-HIV-1 Drug

Author(s): Guangai Xue and Yoko Aida

Volume 4 , Issue 3 , 2010

Page: [188 - 199] Pages: 12

DOI: 10.2174/2212796811004030188

Price: $65


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.

Keywords: HIV-1 Vpr, nuclear import, pre-integration complex (PIC), importin (Imp)- α, anti-HIV-1 therapy, small molecule inhibitor

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