Potential Use of Pharmacological Cyclin-Dependent Kinase Inhibitors as Anti-HIV Therapeutics
Anne Pumfery, Cynthia d. l. Fuente, Reem Berro, Sergei Nekhai, Fatah Kashanchi and Sheng-Hao Chao
Affiliation: George Washington University,School of Medicine; 2300 Eye St., NW; Ross Hall, Rm 552; WashingtonDC, 20037, USA.
Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the anti-viral effects of PCIs have also been observed against various viruses, including human immunodeficiency virus (HIV), herpes simplex virus, and murine leukemia virus. Through the inhibition of CDK2 and 9, the cellular co-factors for HIV-1 Tat transactivation, HIV-1 replication is blocked by two specific PCIs, CYC202 and flavopiridol, respectively. In this article, we will review the inhibitory mechanisms of flavopiridol and CYC202 and discuss their possible usage in AIDS treatment.
Keywords: Flavopiridol, roscovitine, CYC202, P-TEFb, CDK9, CDK2, HIV, Tat
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