RT Journal Article
T1 N′-Phenylacetohydrazide derivatives as potent Ebola virus entry inhibitors with an improved pharmacokinetic profile
A1 García Rubia, Alfonso
A1 Lasala, Fátima
A1 Ginex, Tiziana
A1 Morales Tenorio, Marcos
A1 Olal, Catherine
A1 Heung, Michelle
A1 Oquist Phillips, Mayra Paola
A1 Galindo, Inmaculada
A1 Cuesta Geijo, Miguel Aprimengel
A1 Casasnovas, Jose María
A1 Campillo, Nuria Eugenia
A1 Canales Mayordomo, María Ángeles
A1 Alonso, Covadonga
A1 Martínez, Ana
A1 Muñoz Fontela, César
A1 Delgado, Rafael
A1 Gil, Carmen
AB Ebola virus (EBOV) is a single-strand RNA virus belonging to the Filoviridae family, which has been associated to most Ebola virus disease outbreaks to date, including the West African and the North Kivu epidemics between 2013 and 2022. This unprecedented health emergency prompted the search for effective medical countermeasures. Following up on the carbazole hit identified in our previous studies, we synthetized a new series of compounds, which demonstrated to prevent EBOV infection in cells by acting as virus entry inhibitors. The in vitro inhibitory activity was evaluated through the screening against surrogate models based on viral pseudotypes and further confirmed using replicative EBOV. Docking and molecular dynamics simulations joined to saturation transfer difference-nuclear magnetic reso-nance (STD-NMR) and mutagenesis experiments to elucidate the biological target of the most potent compounds. Finally, in vitro metabolic stability and in vivo pharmacokinetic studies were performed to confirm their therapeutic potential.
PB American Chemical Society
YR 2023
FD 2023-04-27
LK https://hdl.handle.net/20.500.14352/128971
UL https://hdl.handle.net/20.500.14352/128971
LA eng
NO Alfonso Garcia-Rubia, Fátima Lasala, Tiziana Ginex, Marcos Morales-Tenorio, Catherine Olal, Michelle Heung, Paola Oquist, Inmaculada Galindo, Miguel Ángel Cuesta-Geijo, José M. Casasnovas, Nuria E. Campillo, Ángeles Canales, Covadonga Alonso, Ana Martínez, César Muñoz-Fontela, Rafael Delgado, and Carmen Gil Journal of Medicinal Chemistry 2023 66 (8), 5465-5483
NO Agencia Española de Investigación
NO Instituto de Salud Carlos III
NO European Commission Horizon 2020
DS Docta Complutense
RD 26 feb 2026