Feature ArticleThe mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy
Graphical abstract
Schematic diagrams reveal URMC-099 affects nanoART endosomal trafficking and HIV-1 progeny virion production. (A) HIV-1 budding, assembly and maturation in macrophage Rab7 and Rab11 endosomal compartments. (B) NanoATV targets endosomal compartment for storage and inhibits viral maturation at the site of viral assembly. (C) URMC-099 boosts nanoATV antiviral activity through increased nanoATV accumulation in macrophage Rab7 and Rab11 endosomal compartments.
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Funding: This work was supported by the University of Nebraska Foundation which includes individual donations from Dr. Carol Swarts and Frances and Louie Blumkin, the UNMC Vice Chancellor's office and National Institutes of Health grants P01 MH64570, RO1 MH104147 and P30 AI078494 (to H.A.G.) and P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 NS43985, P30 MH062261 and R01 AG043540 (to H.E.G.). The funders have had no role in study design.
Competing interests: H.A.G. and H.E.G. are members of the Scientific Advisory Board of WavoDyne Therapeutics, Inc. that has exclusive rights to URMC-099 development.
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Equal contributions.
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Current Address: Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.
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Current Address: United States Food and Drug Administration, Silver Spring, MD, 20993-0002, USA.