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    Identification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals.

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    Author
    Sampey, Gavin C
    Iordanskiy, Sergey
    Pleet, Michelle L
    DeMarino, Catherine
    Romerio, Fabio
    Mahieux, Renaud
    Kashanchi, Fatah
    Date
    2020-09-23
    Journal
    Viruses
    Publisher
    MDPI AG
    Type
    Article
    Other
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/v12101067
    Abstract
    Human immunodeficiency virus 1 (HIV-1) is the most prevalent human retrovirus. Recent data show that 34 million people are living with HIV-1 worldwide. HIV-1 infections can lead to AIDS which still causes nearly 20,000 deaths annually in the USA alone. As this retrovirus leads to high morbidity and mortality conditions, more effective therapeutic regimens must be developed to treat these viral infections. A key target for intervention for which there are no current FDA-approved modulators is at the point of proviral transcription. One successful method for identifying novel therapeutics for treating infectious diseases is the repurposing of pharmaceuticals that are approved by the FDA for alternate indications. Major benefits of using FDA-approved drugs include the fact that the compounds have well established toxicity profiles, approved manufacturing processes, and immediate commercial availability to the patients. Here, we demonstrate that pharmaceuticals previously approved for other indications can be utilized to either activate or inhibit HIV-1 proviral transcription. Specifically, we found febuxostat, eltrombopag, and resveratrol to be activators of HIV-1 transcription, while mycophenolate was our lead inhibitor of HIV-1 transcription. Additionally, we observed that the infected cells of lymphoid and myeloid lineage responded differently to our lead transcriptional modulators. Finally, we demonstrated that the use of a multi-dose regimen allowed for enhanced activation with our transcriptional activators. © 2020 by the authors.
    Keyword
    HIV
    activator
    eltrombopag
    febuxostat
    inhibitor
    latency
    mycophenolate
    resveratrol
    transcription
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13847
    ae974a485f413a2113503eed53cd6c53
    10.3390/v12101067
    Scopus Count
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