The next generation of HIV/AIDS drugs: novel and developmental antiHIV drugs and targets.
There are presently 42 million people worldwide living with HIV/AIDS, the majority of which have limited access to antiretrovirals. Even if worldwide penetration was possible, our current chemotherapeutic strategies still suffer from issues of cost, patient compliance, deleterious acute and chronic side effects, emerging single and multidrug resistance, and generalized treatment and economic issues. Even our best antiretroviral therapeutic strategy, highly active antiretroviral therapy (HAART), falls short of completely suppressing HIV replication. Therefore, expansion of current therapeutic options by discovering new antiretrovirals and targets will be critical in the coming years. This review addresses the current status of reverse transcriptase and protease inhibitor development, and summarizes the progress in emerging classes of HIV inhibitors, including entry (T-20, T-1249), coreceptor (SCH-C, SCH-D), integrase (beta-Diketos) and p7 nucleocapsid Zn finger inhibitors (thioesters and PATEs). In addition, the processes of virus entry, PIC transport to the nucleus, HIV interaction with nuclear pores, Tat function, Rev function and virus budding (Tsg101 and ubiquitination) are examined, and proof of concept inhibitors and potential antiviral targets discussed.
Turpin
Jim A
JA
HowPin Consulting International, PO Box B Frederick, MD 21705, USA. Howpin@adelphia.net.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D036022:Capsid Proteins / Q000037:antagonists & inhibitors; D015683:Gene Products, gag / Q000037:antagonists & inhibitors; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D015728:Receptors, HIV / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D019065:Virus Assembly / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D036022:Capsid Proteins; D015683:Gene Products, gag; D019428:HIV Integrase Inhibitors; C071884:NCP7 protein, Human immunodeficiency virus 1; D015728:Receptors, HIV; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus