Accueil

@article{doi:10.1128/aac.00083-22,

title = {Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces},

author = {Delphine Lapaillerie and Cathy Charlier and Véronique Guyonnet-Dupérat and Emilie Murigneux and Henrique S. Fernandes and Fábio G. Martins and Rita P. Magalhães and Tatiana F. Vieira and Clémence Richetta and Frédéric Subra and Samuel Lebourgeois and Charlotte Charpentier and Diane Descamps and Benoît Visseaux and Pierre Weigel and Alexandre Favereaux and Claire Beauvineau and Frédéric Buron and Marie-Paule Teulade-Fichou and Sylvain Routier and Sarah Gallois-Montbrun and Laurent Meertens and Olivier Delelis and Sérgio F. Sousa and Vincent Parissi},

url = {https://journals.asm.org/doi/abs/10.1128/aac.00083-22},

doi = {10.1128/aac.00083-22},

year  = {2022},

date = {2022-07-05},

urldate = {2022-07-05},

journal = {Antimicrobial Agents and Chemotherapy},

volume = {0},

number = {0},

pages = {e00083-22},

abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual molecular model. The best compounds were selected for further characterization using both cellular and biochemical approaches, reiterating SARS-CoV-2 entry and the S/ACE2 interaction. We report here two selected hits, bis-indolyl pyridine AB-00011778 and triphenylamine AB-00047476. Both of these compounds can block the infectivity of lentiviral vectors pseudotyped with the SARS-CoV-2 S protein as well as wild-type and circulating variant SARS-CoV-2 strains in various human cell lines, including pulmonary cells naturally susceptible to infection. AlphaLISA and biolayer interferometry confirmed a direct inhibitory effect of these drugs on the S/ACE2 association. A specific study of the AB-00011778 inhibitory properties showed that this drug inhibits viral replication with a 50% effective concentration (EC50) between 0.1 and 0.5 μM depending on the cell lines. Molecular docking calculations of the interaction parameters of the molecules within the S/ACE2 complex from both wild-type and circulating variants of the virus showed that the molecules may target multiple sites within the S/ACE2 interface. Our work indicates that AB-00011778 constitutes a good tool for modulating this interface and a strong lead compound for further therapeutic purposes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi.org/10.1371/journal.pgen.1010286,

title = {A bistable prokaryotic differentiation system underlying development of conjugative transfer competence},

author = {Sandra Sulser and Andrea Vucicevic and Veronica Bellini and Roxane Moritz and François Delavat and Vladimir Sentchilo and Nicolas Carraro and Jan Roelof van der Meer},

doi = {10.1371/journal.pgen.1010286},

year  = {2022},

date = {2022-06-28},

urldate = {2022-06-28},

journal = {Plos Genetics},

volume = {18},

issue = {6},

pages = {e1010286},

abstract = {The mechanisms and impact of horizontal gene transfer processes to distribute gene functions with potential adaptive benefit among prokaryotes have been well documented. In contrast, little is known about the life-style of mobile elements mediating horizontal gene transfer, whereas this is the ultimate determinant for their transfer fitness. Here, we investigate the life-style of an integrative and conjugative element (ICE) within the genus Pseudomonas that is a model for a widespread family transmitting genes for xenobiotic compound metabolism and antibiotic resistances. Previous work showed bimodal ICE activation, but by using single cell time-lapse microscopy coupled to combinations of chromosomally integrated single copy ICE promoter-driven fluorescence reporters, RNA sequencing and mutant analysis, we now describe the complete regulon leading to the arisal of differentiated dedicated transfer competent cells. The regulon encompasses at least three regulatory nodes and five (possibly six) further conserved gene clusters on the ICE that all become expressed under stationary phase conditions. Time-lapse microscopy indicated expression of two regulatory nodes (i.e., bisR and alpA-bisDC) to precede that of the other clusters. Notably, expression of all clusters except of bisR was confined to the same cell subpopulation, and was dependent on the same key ICE regulatory factors. The ICE thus only transfers from a small fraction of cells in a population, with an estimated proportion of between 1.7-4%, which express various components of a dedicated transfer competence program imposed by the ICE, and form the centerpiece of ICE conjugation. The components mediating transfer competence are widely conserved, underscoring their selected fitness for efficient transfer of this class of mobile elements.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{soree_life_2022,

title = {Life history of oysters influences Vibrio parahaemolyticus accumulation in Pacific oysters (Crassostrea gigas )},

author = {Marion Sorée and François Delavat and Christophe Lambert and Solen Lozach and Mathias Papin and Bruno Petton and Delphine Passerini and Lionel Dégremont and Dominique Hervio Heath},

url = {https://onlinelibrary.wiley.com/doi/10.1111/1462-2920.15996},

doi = {10.1111/1462-2920.15996},

issn = {1462-2912, 1462-2920},

year  = {2022},

date = {2022-05-01},

urldate = {2022-05-01},

journal = {Environmental Microbiology},

pages = {1462--2920.15996},

abstract = {Vibrio parahaemolyticus infection in humans is asso- ciated with raw oyster consumption. Evaluation of V. parahaemolyticus presence in oysters is of most interest because of the economic and public health issues that it represents. To explore V. para- haemolyticus accumulation and depuration in adult Crassostrea gigas, we developed a GFP-tagged V. parahaemolyticus strain (IFVp201-gfp+), as well as a rapid and efficient quantification method in C. gigas oysters haemolymph by flow cytometry. Impact of the life history of C. gigas on accumulation and depuration of V. parahaemolyticus IFVp201 was sub- sequently investigated. We found that naive oysters, i.e. grown in controlled facilities with UV treated sea- water, accumulated significantly more IFVp201 than environmental oysters, i.e. grown in intertidal envi- ronment. We hypothesized that environmental oys- ters could have been immune primed, thus could limit V. parahaemolyticus accumulation. Meanwhile, both naive and environmental oysters had similardepuration rates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {An Efficient Chromatin Immunoprecipitation Protocol for the Analysis of Histone Modification Distributions in the Brown Alga Ectocarpus},

author = {Simon Bourdareau and Olivier Godfroy and Josselin Gueno and Delphine Scornet and Susana M. Coelho and Leila Tirichine and Jean Mark Cock},

doi = {doi: 10.3390/mps5030036},

year  = {2022},

date = {2022-04-25},

urldate = {2022-04-25},

journal = {Methods Protoc. },

volume = {36},

issue = {3},

pages = {36},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cancers14071765,

title = {Inhibiting Endothelin Receptors with Macitentan Strengthens the Bone Protective Action of RANKL Inhibition and Reduces Metastatic Dissemination in Osteosarcoma},

author = {Javier Muñoz-Garcia and Jorge William Vargas-Franco and Bénédicte Brounais-Le Royer and Denis Cochonneau and Jérôme Amiaud and Marie-Françoise Heymann and Dominique Heymann and Frédéric Lézot},

url = {https://www.mdpi.com/2072-6694/14/7/1765},

doi = {10.3390/cancers14071765},

issn = {2072-6694},

year  = {2022},

date = {2022-03-30},

urldate = {2022-01-01},

journal = {Cancers},

volume = {14},

number = {7},

pages = {1765},

abstract = {Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}