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

Informazioni relative al progetto

RespiriTB

ID dell’accordo di sovvenzione: 853903

DOI

10.3030/853903

Data della firma CE 8 Maggio 2019

Data di avvio 1 Maggio 2019

Data di completamento 30 Aprile 2027

Finanziato da

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

Costo totale

€ 10 062 900,01

Contributo UE

€ 6 840 000,00

Coordinato da

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands

CORDIS fornisce collegamenti ai risultati finali pubblici e alle pubblicazioni dei progetti ORIZZONTE.

I link ai risultati e alle pubblicazioni dei progetti del 7° PQ, così come i link ad alcuni tipi di risultati specifici come dataset e software, sono recuperati dinamicamente da .OpenAIRE .

Risultati finali

Documents, reports (9)

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.

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.

Pubblicazioni

Peer reviewed articles (3)

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

Autori: Teun van der Klugt, Robin H. G. A. van den Biggelaar, Anno Saris
Pubblicato in: Critical Reviews in Microbiology, Numero 51, 2025, Pagina/e 463-483, ISSN 1040-841X
Editore: Taylor & Francis
DOI: 10.1080/1040841x.2024.2370979

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

Autori: 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
Pubblicato in: npj Drug Discovery, Numero 2, 2025, ISSN 3005-1452
Editore: 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

Autori: 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
Pubblicato in: Microbiology Spectrum, Numero 12, 2024, ISSN 2165-0497
Editore: American Society for Microbiology
DOI: 10.1128/spectrum.03723-23

Non-peer reviewed articles (1)

Host‐directed therapy to combat mycobacterial infections*

Autori: Gül Kilinç, Anno Saris, Tom H. M. Ottenhoff, Mariëlle C. Haks
Pubblicato in: Immunological Reviews, Numero 301/1, 2021, Pagina/e 62-83, ISSN 0105-2896
Editore: Blackwell Publishing Inc.
DOI: 10.1111/imr.12951