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Blocking Nuclear Import of Pre-Integration Complex: An Emerging Anti-HIV-1 Drug Discovery Paradigm

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Abstract:

Although recent progress in highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the emergence of drug-resistant HIV-1 strains and drug toxicity during long-term treatment of HIVinfected patients necessitate the search for new targets that can be used to develop novel antiviral agents. One such target is the nuclear import process of the HIV pre-integration complex (PIC). The ability of HIV-1 using host cell nuclear import machinery to translocate the viral PIC into the cell nucleus is the critical determinant in the replication of the virus in non-dividing cells, such as macrophages. Compounds inhibiting HIV-1 nuclear import may be attractive candidates for novel anti-HIV development. In this review, we will describe the mechanisms of HIV-1 PIC translocation into the nucleus and the structure-function of the viral and cellular factors involved in this process, as well as several classes of novel anti- HIV compounds which target the nuclear import of HIV-1 PIC and effectively block viral replication.

Keywords: AIDS; HIV-1; LEDGF/p75; inhibitors; integrase (IN); matrix protein (MA); pre-integration complex (PIC); protein-protein interaction; viral protein R (Vpr)

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710790416335

Affiliations: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P.R., China.

Publication date: February 1, 2010

More about this publication?
  • 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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