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Enzyme Inhibition in the Treatment of AIDS

By Michael Cochran-Boucher University of Manchester, 2010. Enzyme Inhibition in the Treatment of AIDS. The Lessons of Cancer Chemotherapy. HIV has four distinct stages targeted by specific chemotherapy Attachment to CD4 Receptor Un-coating viral nucleic acid

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Enzyme Inhibition in the Treatment of AIDS

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  1. By Michael Cochran-Boucher University of Manchester, 2010 Enzyme Inhibition in the Treatment of AIDS

  2. The Lessons of Cancer Chemotherapy HIV has four distinct stages targeted by specific chemotherapy • Attachment to CD4 Receptor • Un-coating viral nucleic acid • Cellular multiplication by now integrated provirus • Assembly and LIBERATION of the Progeny

  3. “The Key Strategy in the treatment of AIDS has been to inhibit activity of key enzymes.”www.informahealthcare.com • HIV Protease • Reverse Transcriptase • Integrace

  4. HIV Protease (Nelfinivir) • HIV Protease is an important target enzyme due to the fact that it is the main protein responsible continued infection. • Early X-Chrystalography provided detail of the proteins active site, giving researchers a clear target. • Inhibition of the active site has been a main focus of drug companies and many successful drugs are currently in use. (Biochemisty by Campell & Ferell, 2008) Image: Center for Computaional Research, 2010.

  5. HIV Reverse Transcriptase (AZT) • ImmunogeneticHIV assays have been used to find mutations in the genes of HIV reverse transcriptase. • Researchers have tracked mutations to specific codons. • Today, each of the codons studied have been shown to confer resistance to the various novel analogs of these now traditional treatments: Zidovudine (AZT), Lamivudine (3TC), Didanosine (ddl) and Zalcitabine (ddC) • (U.S. National Institute of health, 2008) The HIV enzyme reverse transcriptase converts the HIV RNA into HIV DNA for integration into a host cell genome. Howard Hughes Medical Institute, 2009.

  6. HIV Integrace (Raltegravir & MK-2048) • One of the most recent enzymes to be identified and worked with is HIV Integrace. • This enzyme is critical for HIV to copy and subsequently work its way inside the host ‘s cellular defences. • (Biochemisty by Campell & Ferell, 2008) Raltegravir was approved for use October 12, 2007 BYU, Chemistry Department, 2010.

  7. Wikipedia's Version of HIV- Protease as a “British Bulldog”!

  8. References: • Image References: • www.informahealthcare.com • Center for Computaional Research, 2010 • BYU, Chemistry Department, 2010 • Howard Hughes Medical Institute, 2009 • Text References: • www.informahealthcare.com • Biochemistry by Campell & Ferell, 2008 • U.S. National Institute of health, 2008 • Strategies in the Treatment of AIDs and Related Diseases: The Lessons of Cancer Chemotherapy: New Drugs. 1992, Vol. 10. 2

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