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    Quest for New Drugs Against HIV-1 Multi-Drug Resistant Proteases

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    Author
    Vernon, Kasey
    0000-0002-6294-503X
    Advisor
    Zhao, Richard Y.
    Date
    2020
    Type
    dissertation
    
    Metadata
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    Abstract
    HIV-1 protease inhibitors (PIs) are the most potent class of drugs in combinational antiretroviral therapies (cART). However, the current therapies are still not adequate due to the emergence of drug resistance. There is still a need for development of more potent PIs. The objective of this study was to search for multi-drug resistant inhibitors to combat HIV-1 and viral resistant proteases. Our lab developed a fission yeast (Schizosaccharomyces pombe) cell-based system that allows large-scale or high-throughput drug screening. We first used a cell growth-based assay to test a drug candidate. We then used a HIV-1 enzymatic assay to confirm it. We explored four batches of potential anti-HIV compounds as well as nine FDA approved PIs. All FDA-approved PIs potentially inhibited HIV-1 PR with 3 small molecule compounds showed minimal inhibitory effects. Results of this study demonstrated the use of fission yeast cell-based system as a means to discover new PIs.
    Description
    Medical and Research Technology
    University of Maryland, Baltimore
    M.S.
    Keyword
    Drug Resistance, Multiple, Viral
    HIV Protease Inhibitors
    HIV-1
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14480
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