Author: Hilimire, Thomas A.; Chamberlain, Jeffrey M.; Anokhina, Viktoriya; Bennett, Ryan P.; Swart, Oliver; Myers, Jason R.; Ashton, John M.; Stewart, Ryan A.; Featherston, Aaron L.; Gates, Kathleen; Helms, Eric D.; Smith, Harold C.; Dewhurst, Stephen; Miller, Benjamin L.
Title: HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells Cord-id: xhvk7wxl Document date: 2017_4_27
ID: xhvk7wxl
Snippet: [Image: see text] The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antivi
Document: [Image: see text] The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus’ life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.
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