2026-06-14T03:46:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/102742024-09-27T20:20:16Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Prado, Silvia
author
Beltran, Manuela
author
Coiras, Mayte
author
Bedoya, Luis M
author
Alcamí, José
author
Gallego, José
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
funder
Red de Investigación Cooperativa en Investigación en Sida (España)
2020-06-04T10:47:33Z
2020-06-04T10:47:33Z
2016-05-01
Biochem Pharmacol. 2016 May 1;107:14-28.
10.1016/j.bcp.2016.02.007
1873-2968
0006-2952
Biochemical pharmacology
26896646
http://hdl.handle.net/20.500.12105/10274
New antiretroviral agents with alternative mechanisms are needed to complement the combination therapies used to treat HIV-1 infections. Here we report the identification of bioavailable molecules that interfere with the gene expression processes of HIV-1. The compounds were detected by screening a small library of FDA-approved drugs with an assay based on measuring the displacement of Rev, and essential virus-encoded protein, from its high-affinity RNA binding site. The antiretroviral activity of two hits was based on interference with post-integration steps of the HIV-1 cycle. Both hits inhibited RRE-Rev complex formation in vitro, and blocked LTR-dependent gene expression and viral transcription in cellular assays. The best compound altered the splicing pattern of HIV-1 transcripts in a manner consistent with Rev inhibition. This mechanism of action is different from those used by current antiretroviral agents. The screening hits recognized the Rev binding site in the viral RNA, and the best compound did so with substantial selectivity, allowing the identification of a new RNA-binding scaffold. These results may be used for developing novel antiretroviral drugs.
eng
Ciprofloxacin (PubChem CID: 2764)
Clomiphene (PubChem CID: 1548953)
Cyproheptadine (PubChem CID: 2913)
Homochlorcyclizine (PubChem CID: 3627)
Human immunodeficiency virus type 1
Mitoxantrone (PubChem CID: 4212)
Neamine (PubChem CID: 72392)
Neomycin B (PubChem CID: 8378)
RNA
Rev
Screen
Transcription
Bioavailable inhibitors of HIV-1 RNA biogenesis identified through a Rev-based screen
journal article
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BioavailableInhibitorsOf_HIV-1_2017.pdf
URL
https://repisalud.isciii.es/bitstreams/abb9903c-0093-4df6-9dc6-6cf8776f2c6e/download
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BioavailableInhibitorsOf_HIV-1_2017.pdf.txt