Cellular Entry of HIV: Evaluation of Therapeutic Targets

Author(s): Stefan Pohlmann, Jacqueline D Reeves.

Journal Name: Current Pharmaceutical Design

Volume 12 , Issue 16 , 2006

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Abstract:

In the absence of a vaccine which could stop the HIV/AIDS pandemic, the development of therapeutic options is of utmost interest. The combined use of inhibitors of reverse transcriptase and protease as highly active antiretroviral therapy (HAART) provided the first effective treatment of HIV/AIDS and significantly decreased the number of AIDS related deaths in industrialized countries. However, the emergence of resistant viruses and the toxic side effects of HAART highlights that novel therapies are urgently required. The inhibition of HIV-1 entry is a promising option. Entry of HIV-1 into target cells involves interactions of the viral envelope protein (Env) with CD4 and a coreceptor, usually CCR5 or CXCR4. Env binding to receptor triggers several conformational rearrangements in Env, which involve the creation and/or exposure of structural intermediates pivotal to fusion of the viral and cellular membranes. Both, cellular receptors and structures in Env associated with membrane fusion are targets for therapeutic intervention. Here, we will discuss how HIV-1 enters cells and introduce strategies how this process can be inhibited.

Keywords: HAART, nucleoside RT inhibitors (NRTIs), CD4 binding, gp120, Cyanovirin-N, CXCR4 inhibitors

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Article Details

VOLUME: 12
ISSUE: 16
Year: 2006
Page: [1963 - 1973]
Pages: 11
DOI: 10.2174/138161206777442155
Price: $58