Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors

Informations projet

RespiriTB

N° de convention de subvention: 853903

DOI

10.3030/853903

Date de signature de la CE 8 Mai 2019

Date de début 1 Mai 2019

Date de fin 31 Octobre 2026

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 10 062 900,01

Contribution de l’UE

€ 6 840 000,00

Coordonné par

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands

CORDIS fournit des liens vers les livrables publics et les publications des projets HORIZON.

Les liens vers les livrables et les publications des projets du 7e PC, ainsi que les liens vers certains types de résultats spécifiques tels que les jeux de données et les logiciels, sont récupérés dynamiquement sur OpenAIRE .

Livrables

Documents, reports (10)

Enzymatic Assay and Characterization of cyt bc1 & bd inhibitors report

The Enzymatic Assay and Characterization of cyt bc1 & bd inhibitors report will describe the assay, conditions and characterisation methodology of the enzymatic assay for testing cytochrome bc1 and cytochrome bd inhibitors.

In vitro activity report for new anti-bacterial compounds

The In vitro activity report for new anti-bacterial compounds will summarize the results of in vitro activity of newly identified compounds within the project against intracellular (MDR)-Mtb strains in human cells.

Purified Mtb cytochrome report

The Purified Mtb cytochrome report will describe the methodology and confirmation of the purified cytochrome bc1, bc1:aa3, and bd

Continuous enzymatic assay and screening report

The continuous enzymatic assay and screening report will describe the assay, conditions and characterisation methodology of the continuous enzymatic assay for testing Mtr inhibitors and the application in the High Throughput Screening campaign.

Decision on final compound FiH

Short summary and scientific explanation on the final decision of the compound that will be used in the FiH. Minutes of the steering committee meeting where this will be decided are included.

In vitro synergy report for current and new anti-bacterial compounds

The in vitro synergy report for current and new anti-bacterial compounds will summarize the results of in vitro synergy between antibiotics currently used in standard TB treatment regimens and newly identified anti-bacterial compounds against intracellular (MDR)-Mtb strains in human cells.

Bactericidal Activity report

The Bactericidal activity Report will describe the methodology used and the results of two-by-two drug combinations by short murine experiments.

Structures of cytochrome report

The Structure of cytochrome report will describe the structures revealed by Structural Biology of cytochrome bc1 and/or bc1:aa3 or bd.

HDT Target Identification and mode of action report

The HDT Target Identification and mode of action report will describe the process, the methodology and summarize the identified of targets and mode of actions of lead Host Directed Therapeutics compounds.

In vitro activity of single HDT compounds report

In vitro activity of single HDT compounds report will summarize the results of in vitro activity of single Host Directed Therapeutics compounds against intracellular MDRMtb strains in human cells

Websites, patent fillings, videos etc. (1)

Website RespiriTB online

The website developed for communication of all RespiriTB activities will be active and online.

Publications

Peer reviewed articles (4)

Host and bacterial lipid metabolism during tuberculosis infections: possibilities to synergise host- and bacteria-directed therapies

Auteurs: Teun van der Klugt, Robin H. G. A. van den Biggelaar, Anno Saris
Publié dans: Critical Reviews in Microbiology, Numéro 51, 2025, Page(s) 463-483, ISSN 1040-841X
Éditeur: Taylor & Francis
DOI: 10.1080/1040841x.2024.2370979

Structural and mechanistic study of a novel inhibitor analogue of M. tuberculosis cytochrome bc1:aa3

Auteurs: Amit K. Verma, Robbert Q. Kim, Dirk A. Lamprecht, Clara Aguilar-Pérez, Sarah Wong, Nicolas Veziris, Alexandra Aubry, José M. Bartolomé-Nebreda, Rodrigo J. Carbajo, Jennefer Wetzel, Meindert H. Lamers
Publié dans: npj Drug Discovery, Numéro 2, 2025, ISSN 3005-1452
Éditeur: Springer Science and Business Media LLC
DOI: 10.1038/s44386-025-00008-3

A high-throughput target-based screening approach for the identification and assessment of <i>Mycobacterium tuberculosis</i> mycothione reductase inhibitors

Auteurs: Natalia Smiejkowska, Lauren Oorts, Kevin Van Calster, Linda De Vooght, Rob Geens, Henri-Philippe Mattelaer, Koen Augustyns, Sergei V. Strelkov, Dirk Lamprecht, Koen Temmerman, Yann G.-J. Sterckx, Davie Cappoen, Paul Cos
Publié dans: Microbiology Spectrum, Numéro 12, 2024, ISSN 2165-0497
Éditeur: American Society for Microbiology
DOI: 10.1128/spectrum.03723-23

The role of cytochrome bc1 inhibitors in future tuberculosis treatment regimens

Auteurs: Clara Aguilar-Pérez, Anne J. Lenaerts, Cristina Villellas, Jerome Guillemont, John Dallow, Hannah Painter, Nicole C. Ammerman, Anis Hassan, Guillaume Golovkine, Laure Brock, Sylvie Sordello, Aurélie Chauffour, Alexandra Aubry, Thi Cuc Mai, Sarah Wong, Taane G. Clark, Kiyean Nam, Jeongjun Kim, Jinho Choi, Marjolein Crabbe, Jorge Esquivias, Nacer Lounis, Bart Stoops, Katie Amssoms, Jose M. Bartolo
Publié dans: Nature Communications, Numéro 16, 2025, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-025-64427-6

Non-peer reviewed articles (1)

Host‐directed therapy to combat mycobacterial infections*

Auteurs: Gül Kilinç, Anno Saris, Tom H. M. Ottenhoff, Mariëlle C. Haks
Publié dans: Immunological Reviews, Numéro 301/1, 2021, Page(s) 62-83, ISSN 0105-2896
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/imr.12951