Pharmacological Cyclin-Dependent Kinase Inhibitors as HIV-1 Antiviral Therapeutics

Author(s): Cynthia de la Fuente, Anil Maddukuri, Kylene Kehn, Shanese Y. Baylor, Longwen Deng, Anne Pumfery, Fatah Kashanchi.

Journal Name: Current HIV Research

Volume 1 , Issue 2 , 2003

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Abstract:

Human immunodeficiency virus type 1 (HIV-1) can infect quiescent cells, however, viral production is restricted to actively proliferating cells. Recent evidence has indicated that HIV-1 viral proteins, Vpr and Tat, perturb the cell cycle to optimize HIV-1 replication. Vpr arrests the cell cycle at G2 by inactivating the cyclin B / cdk1 complex. Tat regulates the cell cycle by altering factors involved in proliferation and differentiation (i.e. the cdk inhibitor p21 / waf1) and associating with cyclin / cdk complexes (i.e. cyclin E / cdk2, cyclin H / cdk7, and cyclin T / cdk9). These studies indicate the importance of host cellular factors, such as cyclin / cdk complexes, in regulating HIV-1 replication and therefore represent novel targets for antiviral therapeutics. Recently, the efficacy of pharmalogical cdk inhibitors (PCIs) in abrogating viral replication has been under development. To date there are 25-30 PCIs that have been synthesized against known cdks, several of which have been shown to inhibit HIV-1 and other AIDS-associated viruses in vitro and in vivo. Targeting these critical cyclin / cdk complexes needed for viral propagation may solve the problems inherent in current HAART therapy, including the emergence of drug-resistant viruses. Thus, PCIs have the potential to become novel therapeutic antiviral drugs that can inhibit HIV-1 transcription and opens the possibility of new avenues of treatment.

Keywords: HIV-1,, Tat,, latency,, cell cycle,, transcription,, pharmalogical cyclin-dependent kinase inhibitors (PCIs),, antiviral drugs

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Article Details

VOLUME: 1
ISSUE: 2
Year: 2003
Page: [131 - 152]
Pages: 22
DOI: 10.2174/1570162033485339
Price: $58

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