title: Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound.
abstract: Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics.
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA; Department of Pharmacology, Howard University, Washington DC 20059, USA.
authors.forename: Kahli A
authors.initials: KA
authors.lastname: Smith
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA.
authors.forename: Xionghao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Sciences, Howard University, Washington DC 20059, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Bolshakov
authors.affiliation: College of Engineering, Howard University, Washington DC 20059, USA.
authors.forename: James
authors.initials: J
authors.lastname: Griffin
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Biochemistry, School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio TX 78229, USA; Enamine LLC, Princeton Corporate Plaza, 7 Deer Park Drive, Ste. M-3 Monmouth Jct., NJ 08852, USA.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kovalskyy
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ivanov
authors.affiliation: Department of Microbiology, College of Medicine, Howard University, Washington DC 20059, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Jerebtsova
authors.affiliation: Department of Pharmacology, Howard University, Washington DC 20059, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Taylor
authors.affiliation: Department of Pharmaceutical Sciences, Howard University, Washington DC 20059, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Akala
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA; Department of Pharmacology, Howard University, Washington DC 20059, USA; Department of Microbiology, College of Medicine, Howard University, Washington DC 20059, USA; Department of Medicine, Howard University, Washington DC 20059, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
keywords: HIV-1; Latency; Nanoparticles; PP1; SMAPP1; Small molecules; Transcription
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