2010-10-06 Matthews_4 - Antivirals HIV Jason Matthews

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Jason Matthews [email protected] Antivirals HIV
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HIV Human immunodeficiency virus ssRNA virus ~ 100 nm in diameter Dense cylindrical nucleoid with: Core proteins Genomic RNA Reverse transcriptase Envelope Lipid membrane derived from host cell outer membrane Covered by glycoproteins GP120 and GP41
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www.medscape.com accessed 09/05 Lifecycle of a Retrovirus HIV binds to cell - CD4-receptor binding site on host T- lymphocytes or macrophages Fuses with cell and injects core, uncoating Reverse transcriptase makes single-strand DNA copy of viral RNA
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Steps in Lifecycle DNA polymerase makes second DNA copy Ribonuclease destroys original RNA Viral DNA (provirus) migrates to nucleus Integrates into cellular DNA (integrase) Provirus remains latent or transcribes genes into RNA Translation of RNA into viral proteins Protease cleaves viral enzymes from precursors Proteins and RNA are assembled into new virions Virus buds from cell surface
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Kill the virus or halt replication Have minimal toxicity to host Prescribed as combination therapy: HIV cocktail It is possible to stop replication of HIV and block spread Challenges: Monocytes (macrophages) remain infected without dying Retroviruses are elusive – latency Viruses can infect a variety of tissues and cells (e.g. CSF) Anti-retroviral agent goals
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Current HIV Drug Therapy Protease Inhibitors - Virally encoded enzymes Reverse transcriptase inhibitors - Nucleoside/nucleotide reverse-transcriptase inhibitors -NRT Is - Non-nucleotide reverse-transcriptase inhibitors -NNRTIs Fusion Inhibitors
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Inhibition of Reverse Transcription RNA virus Reverse transcriptase makes a DNA copy of the RNA so it can infect cells Different kinds of drugs available which inhibit this enzyme: Nucleoside analogs NONnucleoside reverse transcription inhibitors Nucleotide analogs
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www.medscape.com accessed 09/05
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Nucleoside Analogs Crucial for viral replication and unimportant to host cell function
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto.

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2010-10-06 Matthews_4 - Antivirals HIV Jason Matthews

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