Resultados de investigación

Inhibition of SARS-CoV-2 membrane fusion is a highly desired target to combat COVID-19. The interaction between the spike's heptad repeat (HR) regions 1 (HR1) and 2 (HR2) is a crucial step during the fusion process and these highly conserved HR regions constitute attractive targets for fusion inhibitors. However, the relative importance of each subregion of the long HR1-HR2 interface for viral inhibition remains unclear. Here, we designed, produced, and characterized a series of chimeric miniproteins that mimic two different half subdomains of HR1. The proteins were designed as single polypeptide chains that spontaneously fold into antiparallel trimeric helical bundles aimed at structurally imitate the molecular surface of each HR1 half subregion. All the miniproteins folded stably as helical structures and could bind complementary HR2 peptides with moderate affinity. However, only the miniproteins mimicking the N-terminal HR1 half subdomain, but not those imitating C-terminal one, could inhibit cell infection by SARS-COV-2 real viruses in cell cultures. Most interestingly, the inhibitory activity of the miniproteins correlated with their structural stability, but not with their relative binding affinity for HR2 peptides. These results are highly relevant for designing more focused and active fusion inhibitors targeting the highly conserved HR2 region of the Spike., Departamento de Química Física, Facultad de Ciencias, Universidad de Granada. Grupo FQM-171

Grupo SEJ-625. Dpto. Comercialización e Investigación de Mercados.

Dataset used in the manuscript "PTP Over Wide Area Networks With Offset Measurement Outlier Filtering". This dataset contains synchronization accuracy measurements over long distance links using both NTP and PTP, as well as synthetically generated PTP replays used for offline testing. A detailed description of the contents is found in the README.md file at the root of the dataset., European Union, PROACTIF project (Grant Number: 101194239), MICIU/AEI/10.13039/501100011033, PROACTIF project (Grant Number: PCI2025-163223), MICIU/AEI/10.13039/501100011033, AMIGA8 project (Grant Number: PID2021-123930OB-C22), MICIU/AEI/10.13039/501100011033, FPU Ph.D. Fellowship (Grant Number: FPU20/05842), MICIU/AEI/10.13039/501100011033, FPU Ph.D. Fellowship (Grant Number: FPU20/01857)

Dataset accompanying the manuscript Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery , published on a preprint version on Preprints 2020, 2020120358 (doi: 10.20944/preprints202012.0358.v1), and accepted after peer review on Pharmaceutics 2021., This research, including APC charges, was funded by the Spanish Agencia Estatal de Investigación (Ministry of Science and Innovation) and the European Regional Development Fund [grant numbers CTQ2014-56370-R, CTQ2014-53598, and CTQ2017-85658-R]; Fundación Ramón Areces; and the initiative Solidaridad Entre Montañas.

This work is part of Ph.D. thesis by Maria Jose Jimenez-Quesada, and was supported by European Regional Development Fund (ERDF) co-funded projects BFU2011-22779, BFU2016-77243-P, RTC-2015-4181-2 and RTC-2016-4824-2 (Spanish MINECO), P2011-CVI-7487 (Junta de Andalucia) and 201540E065 (CSIC)., The data presented here are related to the research article entitled “Generation of nitric oxide by olive (Olea europaea L.) pollen during in vitro germination and assessment of the S-nitroso- and nitro-proteomes by computational predictive methods” doi:10.1016/j.niox.2017.06.005 (Jimenez-Quesada et al., 2017) [1]. Predicted cysteine S-nitrosylation and Tyr-nitration sites in proteins derived from a de novo assembled and annotated pollen transcriptome from olive tree (Olea europaea L.) were obtained after using well-established predictive tools in silico. Predictions were performed using both default and highly restrictive thresholds. Numerous gene products identified with these characteristics are listed here. An experimental validation of the data, consisting in nano-LC-MS (Liquid Chromatography-Mass Spectrometry) determination of olive pollen proteins after immunoprecipitation with antibodies to anti-S-nitrosoCys and anti-3-NT (NitroTyrosine) allowed identification of numerous proteins subjected to these two post-translational modifications, which are listed here together with information regarding their cross-presence among the predictions., European Union (EU), Spanish MINECO BFU2011-22779 BFU2016-77243-P RTC-2015-4181-2 RTC-2016-4824-2, Junta de Andalucia P2011-CVI-7487, Consejo Superior de Investigaciones Cientificas (CSIC) 201540E065