RT Journal Article
T1 Novel HIV-1 RNA biogenesis inhibitors identified by virtual pharmacophore-based screening
A1 Simba-Lahuasi, Álvaro
A1 Alcamí, José
A1 Beltrán, Manuela
A1 Bedoya Del Olmo, Luis Miguel
A1 Gallego, José
AB 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.
PB Elsevier
YR 2023
FD 2023-08-06
LK https://hdl.handle.net/20.500.14352/125318
UL https://hdl.handle.net/20.500.14352/125318
LA eng
NO Simba-Lahuasi Á, Alcamí J, Beltrán M, Bedoya LM, Gallego J. Novel HIV-1 RNA biogenesis inhibitors identified by virtual pharmacophore-based screening. Biochemical Pharmacology 2023;215:115734. https://doi.org/10.1016/j.bcp.2023.115734.
NO This project was supported by Generalitat Valenciana of Spain(PROMETEO 2021/036 to J.G.), MCIN/AEI/ 10.13039/501100011033of Spain and “ERDF A way of making Europe” (PID2021-124566OB-I00and RTI2018-093935-B-I00 to J.G and PID2021-125978OB-C21 to J.A.),Universidad Catolica ´ de Valencia (predoctoral contract to A.S.-L.), andInstituto de Salud Carlos III (PI19CIII/00004 to J.A.).
NO Generalitat Valenciana
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Universidad Católica de Valencia
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 21 ene 2026