García Rubia, AlfonsoLasala, FátimaGinex, TizianaMorales Tenorio, MarcosOlal, CatherineHeung, MichelleOquist Phillips, Mayra PaolaGalindo, InmaculadaCuesta Geijo, Miguel AprimengelCasasnovas, Jose MaríaCampillo, Nuria EugeniaCanales Mayordomo, María ÁngelesAlonso, CovadongaMartínez, AnaMuñoz Fontela, CésarDelgado, RafaelGil, Carmen2025-12-152025-12-152023-04-27Alfonso 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), 5465-548310.1021/acs.jmedchem.2c01785https://hdl.handle.net/20.500.14352/128971Ebola 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1021/acs.jmedchem.2c01785https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c01785open access547Small molecule inhibitorsDynamicsCiencias23 Química