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dc.contributor.authorSampey, Gavin C
dc.contributor.authorIordanskiy, Sergey
dc.contributor.authorPleet, Michelle L
dc.contributor.authorDeMarino, Catherine
dc.contributor.authorRomerio, Fabio
dc.contributor.authorMahieux, Renaud
dc.contributor.authorKashanchi, Fatah
dc.date.accessioned2020-10-09T15:38:45Z
dc.date.available2020-10-09T15:38:45Z
dc.date.issued2020-09-23
dc.identifier.urihttp://hdl.handle.net/10713/13847
dc.description.abstractHuman 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.en_US
dc.description.urihttps://doi.org/10.3390/v12101067en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofVirusesen_US
dc.subjectHIVen_US
dc.subjectactivatoren_US
dc.subjecteltrombopagen_US
dc.subjectfebuxostaten_US
dc.subjectinhibitoren_US
dc.subjectlatencyen_US
dc.subjectmycophenolateen_US
dc.subjectresveratrolen_US
dc.subjecttranscriptionen_US
dc.titleIdentification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.doi10.3390/v12101067
dc.identifier.pmid32977702
dc.source.journaltitleViruses
dc.source.volume12
dc.source.issue10
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countrySwitzerland


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