A5078249079- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Radiopharmaceutical Chemistry and Applications
- Semiconductor materials and devices
- vaccines and immunoinformatics approaches
- NF-κB Signaling Pathways
- Computational Drug Discovery Methods
- COVID-19 Clinical Research Studies
- Click Chemistry and Applications
- interferon and immune responses
- SARS-CoV-2 detection and testing
- CRISPR and Genetic Engineering
- Medical Imaging and Pathology Studies
- Synthesis and biological activity
- Bacillus and Francisella bacterial research
- Amyotrophic Lateral Sclerosis Research
- Pharmacological Effects of Natural Compounds
- Ferrocene Chemistry and Applications
- RNA regulation and disease
- Hippo pathway signaling and YAP/TAZ
- Complement system in diseases
- Immune Response and Inflammation
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
Institut Pasteur
2004-2025
Centre National de la Recherche Scientifique
2004-2024
Université Paris Cité
2021-2024
Rockefeller University
2014-2021
High Throughput Biology (United States)
2020-2021
Abstract Hippo signaling is an evolutionarily conserved pathway that restricts growth and regeneration predominantly by suppressing the activity of transcriptional coactivator Yap. Using a high-throughput phenotypic screen, we identified potent non-toxic activator In vitro kinase assays show compound acts as ATP-competitive inhibitor Lats kinases—the core enzymes in signaling. The substance prevents Yap phosphorylation induces proliferation supporting cells murine inner ear, cardiomyocytes,...
Abstract SARS-CoV-2 is continually evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of spike protein towards ACE2 resulted mutations, S477N, E484K, and N501Y, be among first selected, explaining convergent “European” (20E-EU1), “British” (501.V1),”South African” (501.V2), ‘‘Brazilian” variants (501.V3). Plotting binding all RBD against their incidence population shows a strong correlation between two....
Abstract SARS-CoV-2 is the causative agent behind COVID-19 pandemic, responsible for over 170 million infections, and 3.7 deaths worldwide. Efforts to test, treat vaccinate against this pathogen all benefit from an improved understanding of basic biology SARS-CoV-2. Both viral cellular proteases play a crucial role in replication. Here, we study proteolytic cleavage proteins two cell line models replication using mass spectrometry identify protein neo-N-termini generated through protease...
Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, monoclonal explorations revealed humoral immunity coordination. Detailed characterization of a hundred memory antibodies uncovered diversity their repertoire antiviral functions. The latter were influenced...
The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance multiple subvariants originating from BA.2, BA.4, and BA.5 Omicron sub-lineages. They harbor a specific set mutations in spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared neutralizing potential antibodies against BA.2.75.2, BQ.1, BQ.1.1, XBB variants, pre-Omicron Delta variant as reference. Sotrovimab retains some activity it did BA.2/BA.5, but...
Out of the results sole large-scale screening for inhibitors SARS-CoV-1 main protease reported in 2013, attempts to improve 3-pyridyl-bearing hits found have been conducted research laboratories, either on this enzyme or more recently closely related SARS-CoV-2 protease. From resulting structural information reported, we sought design analogues featuring some components providing an affinity active site these proteases along with a different scaffold which would allow further...
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive possibly broad-spectrum target drug development as it is essential the virus life cycle highly conserved among betacoronaviruses. Sensitive efficient high-throughput screening methods key discovery. Here we report a gain-of-signal, sensitive cell-based luciferase assay monitor nsp5 activity show that suitable...
Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved repair these lesions, and successful DSB is essential for cell survival after exposure ionizing radiation (IR) other DNA-damaging agents. As such, inhibition potentially efficacious strategy chemo- radiosensitization. Homologous recombination (HR) nonhomologous...
NF-kappa B essential modulator/IKK-gamma (NEMO/IKK-gamma) plays a key role in the activation of pathway response to proinflammatory stimuli. Previous studies suggested that signal-dependent IKK complex involves trimerization NEMO. The minimal oligomerization domain this protein consists two coiled-coil subdomains named Coiled-coil 2 (CC2) and leucine zipper (LZ) (Agou, F., Traincard, Vinolo, E., Courtois, G., Yamaoka, S., Israel, A., Veron, M. (2004) J. Biol. Chem. 279, 27861-27869). To...
Abstract Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide immunoprofiling in COVID-19 convalescents combining serological, cellular monoclonal explorations, revealed humoral immunity coordination. Detailed characterization of a hundred memory antibodies uncovered diversity their repertoire antiviral functions. The latter were influenced...
Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we provide proof concept that native state stabilization TDP-43 a viable effective for treating proteinopathies. Firstly, leveraged Cryo-EM structures fibrils design C-terminal substitutions disrupt aggregation. Secondly, showed these...
The COVID-19 pandemic highlighted the need for antivirals against emerging coronaviruses (CoV). Inhibiting spike (S) glycoprotein-mediated viral entry is a promising strategy. To identify small molecule inhibitors that block downstream of receptor binding, we established high-throughput screening (HTS) platform based on pseudoviruses. We employed three-step process to screen nearly 200,000 molecules. First, identified hits inhibit pseudoviruses bearing SARS-CoV-2 S glycoprotein....
Abstract Resistance to anti‐microbial agents is a world‐wide health threat. Thus, there an urgent need for new treatments. An alternative approach disarm pathogens consists in developing drugs targeting epigenetic modifiers. Bacterial can manipulate regulatory systems of the host bypass defences proliferate and survive. One example Legionella pneumophila , Gram‐negative intracellular pathogen that targets chromatin with specific, secreted bacterial SET‐domain methyltransferase named RomA....
Abstract SARS-CoV-2 is the causative agent behind COVID-19 pandemic, and responsible for over 170 million infections, 3.7 deaths worldwide. Efforts to test, treat vaccinate against this pathogen all benefit from an improved understanding of basic biology SARS-CoV-2. Both viral cellular proteases play a crucial role in replication, inhibitors targeting have already shown success at inhibiting cell culture models. Here, we study proteolytic cleavage proteins two line models replication using...
We have developed a new high-content cytotoxicity assay using live cells, called "ImageTOX." used high-throughput fluorescence microscope system, image segmentation software, and the combination of Hoechst 33342 SYTO 17 to simultaneously score relative size intensity nuclei, nuclear membrane permeability, cell number in 384-well microplate format. then performed screen 12,668 diverse compounds compared results standard assay. The ImageTOX identified similar sets assay, while identifying more...
Summary The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set mutations in spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared neutralizing potential antibodies against BA.2.75.2, BQ.1, BQ.1.1 XBB variants, pre-Omicron Delta variant as reference. Sotrovimab retains some activity BQ.1 it did...
Abstract Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP‐43) is most actively pursued disease‐modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we provide proof concept that native state stabilization TDP‐43 a viable effective for treating proteinopathies. Firstly, leveraged Cryo‐EM structures fibrils design C‐terminal substitutions disrupt aggregation. Secondly, showed these...