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Novel HIV-1 RNA biogenesis inhibitors identified by virtual pharmacophore-based screening.
Simba-Lahuasi, Álvaro; Alcamí, José; Beltrán, Manuela; Bedoya, Luis M; Gallego, José.
Afiliação
  • Simba-Lahuasi Á; CITSAM, Fundación Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2 46001, Valencia, Spain; Escuela de Doctorado, Fundación Universidad Católica de Valencia San Vicente Mártir, Spain.
  • Alcamí J; Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2 28220, Majadahonda, Spain; CIBERINFEC, Instituto de Salud Carlos III, Spain.
  • Beltrán M; Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2 28220, Majadahonda, Spain; CIBERINFEC, Instituto de Salud Carlos III, Spain.
  • Bedoya LM; Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2 28220, Majadahonda, Spain; CIBERINFEC, Instituto de Salud Carlos III, Spain; Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n 28040, Madrid, Spain. Electronic address: lmbedoya@ucm.es.
  • Gallego J; CITSAM, Fundación Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2 46001, Valencia, Spain. Electronic address: jose.gallego@ucv.es.
Biochem Pharmacol ; 215: 115734, 2023 09.
Article em En | MEDLINE | ID: mdl-37549794
The complex between the Rev protein of HIV-1 and the Rev Recognition Element (RRE) within the virus RNA promotes nuclear export of unspliced or incompletely spliced viral transcripts and is required for virus transmission. Here, we have screened a virtual collection of compounds using a pharmacophore based on the chemical similarity of previously characterized inhibitors to identify new chemical scaffolds blocking the RRE-Rev interaction. The best molecules discovered with this strategy inhibited the complex by binding to the RRE and exhibited substantial antiretroviral activity (between 0.582 and 11.3 µM EC50 values) likely associated to inhibitory actions on viral transcription and Rev function. These results have allowed us to identify structural features required for RRE-Rev inhibition as well as to add new compounds to the pool of possible candidates for developing antiretroviral agents based on blockage of HIV-1 RNA biogenesis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: HIV-1 Idioma: En Ano de publicação: 2023 Tipo de documento: Article